Imidazolin-5-one derivative useful as fasn inhibitors for the treatment of cancer

ABSTRACT

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including those mediated by inhibition of fatty acid synthase (FASN) enzyme, such as, cancer, obesity or related discorders, and liver related disorders. Such compounds are represented by formula (I) as follows: 
     
       
         
         
             
             
         
       
     
     wherein L 1 , a, b, m, n, R 1 , R 2 , R 3 , R 4 , and R 5  are defined herein.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application 61/698,125, filed on Sep. 7, 2012, which is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

The present invention is directed to imidazolin-5-one derivatives, pharmaceutical compositions containing them, and their use as FASN inhibitors, in for example, the treatment of cancer, obesity related disorders, and liver related disorders.

BACKGROUND OF THE INVENTION

Fatty acid synthase (FASN) is a key enzyme for the synthesis of long-chain fatty acids from acetyl-coenzyme A (CoA) and malonyl-CoA that uses reduced nicotinamide adenine dinucleotidephosphate as a cofactor. The final step in the de novo synthesis of fatty acids in mammalians is carried out by FASN, a 250 kDa protein containing 7 functional domains. Through an iterative enzymatic reaction, FASN produces palmitate starting from the substrates acetylCoA and malonylCo, using NADPH (as defined below) as a cofactor (See, MAIER, T., et al., “Architecture of mammalian fatty acid synthase at 4.5 Å resolution”, Science, 2006, pp 1258-1262, Vol. 311).

FASN is minimally expressed in most normal human tissues except the liver and adipose tissue, where it is expressed at high levels. Except for these lipogenic tissues (such as liver, lactating breast, fetal lung, and adipose tissue), FASN has a low expression in normal cells which use fatty acids from the diet, while tumor cells largely depend on de novo fatty acid synthesis. FASN expression is highly up-regulated in various tumors, e.g. prostate, breast, colon, and lung cancer (See, SWINNEN, J. V., et al., “Stimulation of tumor-associated fatty acid synthase expression by growth factor activation of the sterol regulatory element-binding protein pathway”. Oncogene, 2000, pp 5173-5181, Vol 19; KUHAJA, F. P., “Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology”, Nutrition, 2000, pp 202-208, Vol. 16).

FASN overexpression leads to growth and survival advantage to the tumors achieved through multiple mechanisms. Firstly, it provides lipids for membrane synthesis. Moreover, the more saturated lipid composition of the membranes increases resistance to chemotherapy. FASN also contributes to improved growth factor receptor expression in lipid rafts (See, SWINNEN, J. V., et al., “Fatty acid synthase drives the synthesis of phospholipids partitioning into detergent resistant membrane microdomains”, Biochem. Biophys. Res. Commun., 2000, pp 898-903, Vol. 302; MENENDEZ, J. A., et al., “Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells”, Proc. Natl Acad. Sci. USA, 2004, pp 10715-10720, Vol. 101), and improved cell signalling. Lastly, the NAPDPH consumption during palmitate synthesis in tumor cells keeps the redox balance in check.

In tumor cells, but not in normal cells, siRNA knock down or pharmacological inhibition of FASN results in apoptosis in vitro, and in a delayed tumor growth in vivo. The role of FASN as a potential oncogene has been further established in mouse models. Transgenic mouse models with FASN over expression in the prostate develop invasive prostate cancer in the presence of Androgen Receptor (See, MIGITA, et a., “Fatty Acid Synthase: A Metabolic Enzyme and Candidate Oncogene in Prostate Cancer”, JNatl. Cancer Inst., 2009, pp 519-532, Vol. 101). It has been proposed that FASN exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis. Androgens and epidermal growth factor (EGF) up-regulate FASN expression and activity. In addition, FASN is also over expressed in androgen-independent prostate cancers most likely through activation of the PI3K/Akt pathway (See, BANDYOPADHYAY, S., et al., “FAS expression inversely correlates with PTEN level in prostate cancer and a PI-3 kinase inhibitor synergizes with FAS siRNA to induce apoptosis”, Oncogene, 2005, pp 5389-5395, Vol. 24; VAN DE DANDE, T., et al., “Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in the overexpression of fatty acid synthase in LNCaP prostate cancer cells”, Cancer Res., 2002, pp 642-646, Vol. 62; PORTSMANN, T., et al., “PKB/AKT induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP”, Oncogene, 2005, pp 6465-6481, Vol. 24). Thus, FASN is emerging as an important target for cancer therapy.

Since FASN expression is markedly increased in several human cancers compared with the corresponding normal tissue, and FASN overexpression in tumors has been associated with a poor prognosis, FASN inhibitors are viewed as potential therapeutics for the treatment of cancer. There remains a need for pharmaceutical agents for the treatment of a variety of cancers, including breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, blood, bone, and others.

FASN inhibitors have also shown promise in the treatment of other FASN-mediated diseases, disorders or conditions, such as, obesity, lack of appetite control, and inflammatory conditions. Additionally, FASN has been implicated in diabetes and/or regulation of the general wellness of the liver, and therefore has potential in the treatment of obesity, Type II diabetes mellitus, Syndrome X, and disorders of the liver; the treatment of which there remains a need for pharmaceutical agents.

SUMMARY OF THE INVENTION

The present invention is directed to compounds of formula (I)

wherein

R¹ and R² are taken together with the carbon atom to which they are bound to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₈cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one to two R¹¹ groups;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one to two R¹¹ groups;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains one heteroatom selected from the group consisting of O, S and N; wherein the S is optionally substituted with one to two oxo; wherein the N is substituted with R¹⁰; provided that the heteroatom is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl is optionally substituted with one R¹¹ group, and further optionally substituted with one R¹² group;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₂₋₄alkyl)-O—(C₁₋₄alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₃alkyl)-NR^(A)R^(B), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(A)R^(B), phenyl and 5 to 6-membered heteroaryl;

-   -   wherein Z¹ is selected from the group consisting of —CH₂—, —O—,         —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(A), R^(B) and         R^(C) are each independently selected from the group consisting         of hydrogen and C₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(A)R^(B), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein each R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)OH, —C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(D)R^(E), phenyl and 5 to 6-membered heteroaryl;

wherein Z² is selected from the group consisting of —CH₂—, —O—, —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(D), R^(E) and R^(F) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl, whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(D)R^(E), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

and wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and hydroxy substituted C₁₋₄alkyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-2S-yl, and piperidin-4-yl;

a is an integer from 0 to 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR^(L)—, —C(S)—, —SO₂—, —SO₂—NR^(L)—; wherein R^(L) is selected from the group consisting of hydrogen and C₁₋₄alkyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), 4 to 6-membered, saturated heterocyclyl, —(C₁₋₄alkyl)-(4 to 6-membered, saturated heterocyclyl), —(C₂₋₄alkenyl)-(5 to 6-membered, saturated heterocyclyl), 5 to 6-membered heteroaryl, —(C₁₋₄alkyl)-(5 to 6-membered heteroaryl), —(C₂₋₄alkenyl)-(5 to 6-membered heteroaryl), and NR^(V)R^(W); wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein the C₃₋₆cycloalkyl, 4 to 6-membered saturated heterocyclyl or 5 to 6-membered heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₄alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 2;

each R⁴ is independently selected from the group consisting of hydroxy, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, cyano, and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; provided that each R⁴ group is bound to a carbon atom;

provided that when

is selected from the group consisting of

and substituted with —(R⁴)_(b), then b is an integer from 0 to 1;

R⁵ is selected from the group consisting of

selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-CN, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —NR^(M)R^(N), —(C₁₋₄alkyl)-NR^(P)R^(Q), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, —NR^(M)—C(O)—(C₁₋₄alkyl), —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₆cycloalkyl, -cyano-(C₃₋₆cycloalkyl), —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), —S—(C₃₋₆cycloalkyl), —SO—(C₃₋₆cycloalkyl), —SO₂—(C₃₋₆cycloalkyl), —NH—(C₃₋₆cycloalkyl), —NH—SO₂—(C₃₋₆cyclalkyl), oxetanyl, —(C₁₋₂alkyl)-oxetanyl, tetrahydofuranyl, —(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl, and —(C₁₋₂alkyl)-tetrahydro-pyranyl;

wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein R^(P) and R^(Q) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; alternatively R^(P) and R^(Q) are taken together with the nitrogen atom to which they are bound to form a 5 to 6-membered saturated heterocyclyl; such 5 to 6-membered saturated heterocyclyl is optionally substituted with a substituent selected from the group consisting of halogen, C₁₋₄alkyl and fluorinated C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(R)R^(S), —C(O)—NR^(R)R^(S), —C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R^(R) and R^(S) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein

is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, —(C₁₋₂alkyl)-oxetanyl, tetrahydofuranyl, —(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl and —(C₁₋₂alkyl)-tetrahydro-pyranyl; wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point

of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃ or —SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl) and 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl and 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl or 6-(morpholin-4-yl)-pyridin-3-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl or 4-(3-chlorophenyl)-phenyl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl;

provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl;

and stereoisomers, tautomers, and pharmaceutically acceptable salts thereof.

The present invention is further directed to processes for the preparation of the compounds of formula (I), as described in more detail in the general synthesis schemes and examples below. The present invention is further directed to a product prepared according to any of the processes as described in the general synthesis schemes and examples below.

The present invention is further directed to intermediates in the synthesis of the compounds of formula (I), including, but not limited to, compounds of formula (XVIII), compounds of formula (XXI), compounds of formula (XXIII), compounds of formula (XXV) and compounds of formula (XXVII), as described in more detail below.

Illustrative of the invention is a pharmaceutical composition comprising, consisting of and/or consisting essentially of a pharmaceutically acceptable carrier and the product prepared according to the process described herein. An illustration of the invention is a pharmaceutical composition made by mixing the product prepared according to the process described herein and a pharmaceutically acceptable carrier. Illustrating the invention is a process for making a pharmaceutical composition comprising, consisting of, and/or consisting essentially of mixing the product prepared according to the process described herein and a pharmaceutically acceptable carrier.

Exemplifying the invention are methods of treating a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme (selected from the group consisting of cancer, obesity and related disorders, and liver related disorders, as defined below) comprising, consisting of, and/or consisting essentially of administering to a subject in need thereof a therapeutically effective amount of any of the compounds or pharmaceutical compositions described above.

In an embodiment, the present invention is directed to a compound of formula (I) for use as a medicament. In another embodiment, the present invention is directed to a compound of formula (I) for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme (selected from the group consisting of cancer, obesity and related disorders, and liver related disorders, as defined below). In another embodiment, the present invention is directed to a composition comprising a compound of formula (I) for the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme (selected from the group consisting of cancer, obesity and related disorders and liver related disorders, as herein below).

Another example of the invention is the use of any of the compounds described herein in the preparation of a medicament for treating: (a) cancer, as defined below, (b) obesity or related disorder, (c) liver related disorder, in a subject in need thereof.

In another example, the present invention is directed to a compound as described herein for use in a methods for treating a disorder selected from the group consisting of cancer, obesity and related disorders, and liver related disorders, as herein defined, in a subject in need thereof.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to compounds of formula (I)

wherein R¹, R², R³, R⁴, R⁵, L¹, a, b, m, n,

are as herein defined. The compounds of the present invention are FASN inhibitors useful in the treatment of, for example, cancer. More particularly, the compounds of formula (I) of the present invention are useful in the treatment of FASN-mediated disorders including, but not limited to, (a) cancer, as herein defined, (b) obesity and related disorders and (c) liver related disorders, as herein defined.

In a preferred embodiment, the present invention is directed to methods for the treatment of cancer comprising, consisting of, and/or consisting essentially of administering to a subjected in need thereof, a therapeutically effective amount of a compound of formula (I); wherein the cancer is selected from the group consisting of cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood, and bone. Preferably, the cancer is selected from the group consisting of breast, prostate, colon, lung, brain, spinal cord, ovary, endometrium, thyroid, kidney, and stomach.

In another embodiment, the cancer is selected from the group consisting of glioma, glioblastoma, leukemia, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast cancer, inflammatory breast cancer, Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma, ependymoma, medulloblastoma, sarcoma, osteosarcoma, melanoma, giant cell tumor of bone, and giant cell tumor of thyroid.

In another embodiment, the present invention is directed to methods for the treatment of obesity or a related disorder comprising, consisting of, and/or consisting essentially of administering to a subjected in need thereof, a therapeutically effective amount of a compound of formula (I); wherein the obesity or related disorder is selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, appetite and/or satiety modulation. Preferably, the obesity or related disorders is selected from the group consisting of obesity, Type II diabetes mellitus, Syndrome X, and appetite and/or satiety modulation, more preferably obesity or Type II diabetes mellitus.

In another embodiment, the present invention is directed to methods for the treatment of an liver related disorder comprising, consisting of, and/or consisting essentially of administering to a subjected in need thereof, a therapeutically effective amount of a compound of formula (I); wherein the liver related disorder is selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty libver, non-alcoholic steatohepatitis (NASH), fatty liver, and/or non-alcoholic fatty liver disease (NAFLD). Preferably, the liver related disorder is selected from dylipidemia or elevated cholestrol levels.

In an embodiment, the present invention is directed to a pharmaceutical composition comprising, consisting of, and/or consisting essentially of a pharmaceutically acceptable carrier and a compound of formula (I). In another embodiment, the present invention is directed to a pharmaceutical composition made by mixing a compound of formula (I) and a pharmaceutically acceptable carrier. In another embodiment, the present invention is directed to a process for making a pharmaceutical composition comprising mixing a compound of formula (I) and a pharmaceutically acceptable carrier.

In an embodiment, the present invention is directed to a method of treating a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, comprising, consisting of, and/or consisting essentially of administering to a subject in need thereof a therapeutically effective amount of the compound of formula (I).

In another embodiment, the present invention is directed to a method of treating a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, wherein the disorder mediated by inhibition of fatty acid synthase (FASN) enzyme is a cancer selected from the group consisting of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood, and bone.

In another embodiment, the present invention is directed to a method of treating a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, wherein the disorder mediated by inhibition of fatty acid synthase (FASN) enzyme is selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation.

In another embodiment, the present invention is directed to a method of treating a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, wherein the disorder mediated by inhibition of fatty acid synthase (FASN) enzyme is selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD).

In an embodiment, the present invention is directed to a method of treating (a) cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; or (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD); comprising, consisting of, and/or consisting essentially of administering to a subject in need thereof, a therapeutically effective amount of the compound of formula (I).

In another embodiment, the present invention is directed to a method of treating (a) cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; or (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD); comprising, consisting of, and/or consisting essentially of administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I).

In an embodiment, the present invention is directed to the use of a compound formula (I) for the preparation of a medicament for treating: (a) cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; or (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD); in a subject in need thereof.

In another embodiment, the present invention is directed to the use of a compound of formula (I), for use in a method for treating a disorder selected from the group consisting of (a) cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; or (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD); in a subject in need thereof.

In another embodiment, the present invention is directed to a compound of formula (I) for use as a medicament. In another embodiment, the present invention is directed to a compound of formula (I) (as in claim 1) for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme. In another embodiment, the present invention is directed to a compound of formula (I), for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, selected from the group consisting of cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone. In another embodiment, the present invention is directed to a compound of formula (I), for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, selected from (a) obesity and related disorders or (b) liver related disorders.

In an embodiment, the present invention is directed to a composition comprising, consisting of, and/or consisting essentially of a compound of formula (I) for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme.

In another embodiment, the present invention is directed to a composition comprising, consisting of, and/or consisting essentially of compound of formula (I) for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme selected from the group consisting of (a) cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood or bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; and (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD).

In an embodiment, the present invention is directed to compounds of formula (I)

wherein

R¹ and R² are taken together with the carbon atom to which they are bound to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₈cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one to two R¹¹ groups;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one to two R¹¹ groups;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains one heteroatom selected from the group consisting of O, S and N; wherein the S is optionally substituted with one to two oxo; wherein the N is substituted with R¹⁰; provided that the heteroatom is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl is optionally substituted with one R¹¹ group, and further optionally substituted with one R¹² group;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₂₋₄alkyl)-O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₃alkyl)-NR^(A)R^(B), —C(O)—(C₁₋₄alkyl), —C(O)—(C₃₋₆cycloalkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(A)R^(B), phenyl and 5 to 6-membered heteroaryl;

wherein Z¹ is selected from the group consisting of —CH₂—, —O—, —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(A)R^(B), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein each R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)OH, —C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(D)R^(E), phenyl and 5 to 6-membered heteroaryl;

wherein Z² is selected from the group consisting of —CH₂—, —O—, —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(D), R^(E) and R^(F) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(D)R^(E), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, and fluorinated C₁₋₄alkoxy;

and wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and hydroxy substituted C₁₋₄alkyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, and piperidin-4-yl;

a is an integer from 0 to 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)—NR^(L)—, —C(S)—, —SO₂—, and —SO₂—NR^(L)—; wherein R^(L) is selected from the group consisting of hydrogen and C₁₋₄alkyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), 5 to 6-membered, saturated heterocyclyl, —(C₁₋₄alkyl)-(5 to 6-membered, saturated heterocyclyl), —(C₂₋₄alkenyl)-(5 to 6-membered, saturated heterocyclyl), 5 to 6-membered heteroaryl, —(C₁₋₄alkyl)-(5 to 6-membered heteroaryl), and —(C₂₋₄alkenyl)-(5 to 6-membered heteroaryl);

wherein the C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 2;

each R⁴ is independently selected from the group consisting of hydroxy, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, cyano, and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; provided that each R⁴ group is bound to a carbon atom;

provided that when

is selected from the group consisting of

and substituted with —(R⁴)_(b), then b is an integer from 0 to 1;

R⁵ is selected from

selected from the group consisting of aryl, heteroaryl, and partially unsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(M)R^(N), —(C₁₋₄alkyl)-NR^(P)R^(Q), —C(O)—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, —NR^(M)—C(O)—(C₁₋₄alkyl), and —NR^(M)—SO₂—(C₁₋₄alkyl);

wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein R^(P) and R^(Q) are each independently selected from hydrogen or C₁₋₄alkyl; alternatively R^(P) and R^(Q) are taken together with the nitrogen atom to which they are bound to form a 5 to 6-membered saturated heterocyclyl; such 5 to 6-membered saturated heterocyclyl is optionally substituted with a substituent selected from the group consisting of halogen, C₁₋₄alkyl, and fluorinated C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(R)R^(S), —C(O)—NR^(R)R^(S), —C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R^(R) and R^(S) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein

is selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and —(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer, and a pharmaceutically acceptable salt thereof.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one R¹¹ group;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered, saturated heterocyclyl contains O or NR¹⁰; provided that the O or NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 6-membered, saturated heterocyclyl containing the O or NR¹⁰ is optionally substituted with one R¹¹ group and further optionally substituted with one R¹²;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —(C₂alkyl)-O—(C₁₋₄alkyl), —C(O)O—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl),

—C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl); wherein Z¹ is selected from the group consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄alkyl);

wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substituted C₁₋₂alkyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 0;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl, piperidin-3R-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR^(L)- and —SO₂—; wherein R^(L) is selected from the group consisting of hydrogen and methyl;

R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl;

wherein the C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₂alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; provided that the R⁴ group is bound to a carbon atom;

R⁵ is selected from the group consisting of

selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, cyano substituted (C₁₋₄alkyl), —(C₁₋₂alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₅cycloalkyl, 1-cyano-(C₃₋₅cycloalkyl), —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—(C₃₋₅cycloalkyl), —NH—SO₂—(C₃₋₅cycloalkyl), oxetanyl and tetrahydro-furanyl;

wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein

is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one R¹¹ group;

(b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group;

and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains O or NR¹⁰; provided that the O or NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl containing the O or NR¹⁰ is optionally substituted with one R¹¹ group and further optionally substituted with one R¹²;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₄alkyl), —C(O)—(C₃₋₆cycloalkyl),

wherein Z¹ is selected from the group consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B) and R^(D) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄alkyl);

wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substituted C₁₋₂alkyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)—NR^(L)— and —SO₂—; wherein R^(L) is selected from the group consisting of hydrogen and methyl;

R³ is selected from the group consisting of C₂₋₄alkenyl, C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl and 5 to 6-membered heteroaryl;

wherein the C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; provided that the R⁴ group is bound to a carbon atom;

R⁵ is selected from the group consisting of

selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₄alkyl);

wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

d is an integer from 0 to 1;

R⁷ is selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy;

wherein

is selected from the group consisting of phenyl and 5 to 6-membered heteroaryl;

e is an integer from 0 to 2;

each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and —(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₆cycloalkyl; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxy substituted C₁₋₂alkyl), —CH₂-(phenyl), —(C₂alkyl)-O—(C₁₋₂alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl), —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl), wherein R^(A) and R^(B) are each independently selected from the group consisting of hydrogen and methyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2 provide that when n is 2, then m is 0

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-3S-yl, and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, fluorinated C₁₋₂alkyl, C₂₋₄alkenyl, C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein the C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl is optionally substituted with a substituent selected from the group consisting of halogen, hydroxy, C₁₋₂alkyl, (C₁₋₂alkyl)-OH, fluorinated C₁₋₂alkyl, cyano and NH₂; and wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and methyl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy;

R⁵ is selected from the group consisting of

selected from the group consisting of phenyl, naphthyl, 5 to 6-membered heteroaryl, 9 to 10-membered heteroaryl and partially unsaturated 9 to 10-membered heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, cyano-substituted C₁₋₂alkyl, —(C₁₋₂alkyl)-O—(C₁₋₂alkyl), C₁₋₄alkoxy, fluorinated C₁₋₂alkoxy, —SO₂—(C₁₋₄alkyl), —CO²H, —C(O)O—(C₁₋₂alkyl), —C(O)—(C₁₋₂ alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₂alkyl), C₃₋₅cycloalkyl, 1-cyano-cyclopropyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—C(O)—(C₃₋₅cycloalkyl) and —NH—SO₂—(C₃₋₅cycloalkyl) and oxetan-3-yl; and wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl;

wherein

is selected from the group consisting of phenyl and 6-membered, nitrogen containing heteroaryl;

wherein

is selected from the group consisting of phenyl, 5 to 6-membered, saturated, nitrogen containing heterocylyl and 5 to 6-membered, nitrogen containing heteroaryl;

e is an integer from 0 to 1;

R⁸ is selected from the group consisting of halogen, C₁₋₄alkyl, C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl) and oxetanyl;

provided that the

is bound at the 3- or 4-position of the

relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein,

R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of

(a) C₃₋₆cycloalkyl; and

(c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one;

wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₂alkyl), —CH₂-(phenyl), —C(O)—(C₁₋₄alkyl), —C(O)-(cyclopropyl) and —C(O)—NR^(A)R^(B); wherein R^(A) and R^(B) are each independently selected from the group consisting of hydrogen and methyl;

m is an integer from 0 to 1;

n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)— and —SO₂—;

R³ is selected from the group consisting of C₂alkenyl, C₃cycloalkyl, 5-membered, saturated heterocyclyl and 5-membered heteroaryl; wherein the C₃cycloalkyl, 5-membered, saturated heterocyclyl or 5-membered heteroaryl is optionally substituted with a substituent selected from the group consisting of halogen, C₁₋₂alkyl, fluorinated C₁₋₂alkyl and cyano;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy;

R⁵ is selected from the group consisting of

selected from the group consisting of phenyl, heteroaryl and partially unsaturated heterocyclyl;

c is an integer from 0 to 2;

each R⁶ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₂alkyl, fluorinated C₁₋₂alkyl, C₁₋₂alkoxy, fluorinated C₁₋₂alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₂alkyl), —NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₂alkyl); and wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl;

wherein

is phenyl;

wherein

is selected from the group consisting of phenyl and 5 to 6-membered, nitrogen containing heteroaryl;

e is an integer from 0 to 1;

R⁸ is selected from the group consisting of halogen and C₁₋₂alkyl;

provided than when

is phenyl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)piperidin-4,4-diyl, 1-(ethenyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)piperidin-4,4-diyl, 1-(2-methoxy-ethyl)piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl and 1-(methoxycarbonyl)-azetidin-3,3-diyl;

m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2 then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3R-yl, piperidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of methyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl. 3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino, dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, and pyridin-3-yl;

is selected from the group consisting of

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyl and 2-methoxy;

R⁵ is selected from the group consisting of

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2-fluoro-4-(1-cyano-cuclopropyl)-phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl, 4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl 3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl, 3-(cyclopropylcarbonyl-amino)-phenyl, 3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl, 3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl, 3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl, 6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl, 7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl, 6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cycloprpoyl-pyridin-3-yl, 6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl, 5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, 1-(trifluoromethyl-carbonyl)indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl, 2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl, 2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl, 2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl, 3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl, 4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl, 2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl, 2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl, 6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl, quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl, 1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-7-methoxymethyl-indazol-4-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-7-hydroxymethyl-indazol-4-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl, 2-methyl-3-hydroxymethyl-indazol-5-yl, 2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl, 2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl, 1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl, 2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl, 1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydro-benzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, 1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl, 1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl, [1,2,4]triazo[4,3-a]pyridin-6-yl, 3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl and 4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl;

is selected from the group consisting of phenyl, pyridin-3-yl and pyridin-4-yl;

and

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl, 1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl, pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, and 1-(oxetan-3-yl)-pyrazol-4-yl;

provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the point of attachment of the

to the

provided further that when

is pyridin-4-yl, then

is bound to

at the 3-position, relative to the point of attachment of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein,

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of —C(O)— and —SO₂—; R³ is selected from the group consisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl and tetrahydro-furan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyl and 2-methoxy; R⁵ is selected from the group consisting of

is selected from the group consisting of 4-(3-cyano-phenyl), 4-(4-cyano-phenyl), 4-(3-hydroxy-phenyl), 4-(4-hydroxy-phenyl), 4-(3-fluoro-phenyl), 4-(4-fluoro-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl), 4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl), 4-(4-methyl-phenyl), 4-(3-trifluoromethyl-phenyl), 4-(4-trifluoromethyl-phenyl), 4-(2-methoxy-phenyl), 4-(3-methoxy-phenyl), 4-(4-methoxy-phenyl), 4-(3-trifluoromethoxy-phenyl), 4-(4-trifluoromethoxy-phenyl), 4-(3-dimethylamino-phenyl), 4-(4-dimethylamino-phenyl), 4-(3-methylsulfonyl-amino-phenyl), 4-(3-amino-4-hydroxy-phenyl), 4-(3-formamido-4-hydroxy-phenyl), 4-(pyridin-2-yl), 4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl), 4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl), 4-(quinolin-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl), 4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl), 4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl), 4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl), 4-(benzimidazol-5-yl), 4-(benzoxazol-2-yl), 4-(benzoxazol-5-yl), 4-(benzthiazol-5-yl), 4-(2,3-dimethyl-benzothiophen-5-yl), 4-(1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl) and 4-(1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl);

is 4-(phenyl);

and

is selected from the group consisting of 4-(4-bromo-phenyl), 4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl), 4-(tetrazol-5-yl) and 3-(pyrazol-3-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(ethenylcarbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl and tetrahydro-pyran-4,4-diyl;

m is an integer from 0 to 1; and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of ethyl, 1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl, 3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, oxetan-2-yl, oxetan-3yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl and dimethylamino;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro and 3-methyl;

R⁵ is

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, 3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl, 6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl, 6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl, 2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, 2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl and pyrrolo[2,3-b]pyridin-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-methyl-cyclopropyl, pyrrolidin-1-yl and 1-methyl-pyrazol-3-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyl and 2-methoxy; R⁵ is

is selected from the group consisting of 4-(4-cyano-phenyl), 4-(3-hydroxy-phenyl), 4-(4-hydroxy-phenyl), 4-(3-fluoro-phenyl), 4-(4-fluoro-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl), 4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl), 4-(4-methyl-phenyl), 4-(3-trifluoromethyl-phenyl), 4-(3-methoxy-phenyl), 4-(4-methoxy-phenyl), 4-(3-dimethylamino-phenyl), 4-(4-dimethylamino-phenyl), 4-(3-methylsulfonyl-amino-phenyl), 4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl), 4-(quinolin-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl), 4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl), 4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl), 4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl), 4-(benzoxazol-2-yl), 4-(benzoxazol-5-yl), 4-(benzthiazol-5-yl) and 4-(2,3-dimethyl-benzothiophen-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl;

m is an integer from 0 to 1: and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl, cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro and 3-methyl;

R⁵ is

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indaozl-5-yl, 1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyl and 2-methoxy; R⁵ is

is selected from the group consisting of 4-(4-cyano-phenyl), 4-(3-hydroxy-phenyl), 4-(4-fluoro-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl), 4-(2,4-dichloro-phenyl), 4-(3-methyl-phenyl), 4-(4-methyl-phenyl), 4-(3-methoxy-phenyl), 4-(4-methoxy-phenyl), 4-(4-dimethylamino-phenyl), 4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(isoquinolin-5-yl), 4-(isoquinolin-6-yl), 4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl), 4-(1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl), 4-(benzofuran-5-yl), 4-(2-methyl-benzofuran-5-yl), 4-(benzthiazol-5-yl) and 4-(2,3-dimethyl-benzothiophen-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrfuran-2S-yl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro and 2-methyl;

R⁵ is

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl, isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 1; n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro and 2-methyl; R⁵ is

is selected from the group consisting of 4-(3-hydroxy-phenyl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(isoquinolin-6-yl), 4-(indazol-4-yl), 4-(1-methyl-indazol-5-yl), and 4-(benzofuran-5-yl) and 4-(benzthiazol-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is selected from the group consisting of

is selected from the group consisting of naphtha-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl and 1-methyl-benzimidazol-5-yl;

wherein

is selected from the group consisting of pyridin-4-yl and 1-methyl-pyrazol-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl and 1-(benzyl)piperidin-4,4-diyl; m is an integer from 0 to 1; n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

b is an integer from 0 to 1; R⁴ is 2-methyl; R⁵ is

is selected from the group consisting of 4-(4-cyano-phenyl), 4-(3-hydroxy-phenyl), 4-(3-chloro-phenyl), 4-(4-chloro-phenyl), 4-(4-methyl-phenyl), 4-(4-methoxy-phenyl), 4-(indol-4-yl), 4-(indol-5-yl), 4-(indol-6-yl), 4-(quinolin-5-yl), 4-(isoquinolin-6-yl), 4-(isoquinolin-7-yl), 4-(indazol-4-yl), 4-(indazol-5-yl), 4-((1-methyl-indazol-5-yl), 4-(1-methyl-indazol-6-yl), 4-(benzofuran-5-yl) and 4-(benzthiazol-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

is selected from the group consisting of 4-(indol-5-yl), 4-(indol-6-yl), 4-(isoquinolin-6-yl) and 4-(benzofuran-5-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl and tetrahydropyran-4,4-diyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is selected from the group consisting of

is selected from the group consisting of naphth-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl, benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzimidazol-5-yl and 1-methyl-benzimidazol-5-yl;

wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl and pyridin-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, 1-methyl-cyclobutyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl and oxetan-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro, 2-chloro and 2-methyl;

R⁵ is selected from the group consisting of

is selected from the group consisting of 3-(cyclopropyl-sulfonylamino)-phenyl, naphth-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 2-methyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 8-fluoro-quinolin-2-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 2-methyl-benzothien-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl and 1-methyl-benzimidazol-5-yl;

wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl and 1-cyclobutyl-pyrazol-4-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form cyclopropyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is cyclopropyl;

is selected from the group consisting of

b is 0;

R⁵ is

is selected from the group consisting of indol-5-yl, indol-6-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl, benzofuran-5-yl, benzothien-5-yl and 6-cyano-naphth-2-yl;

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl, 1-(isopropylcarbonyl)-piperidin-4,4-diyl, 1-(2-hydroxyethyl)-piperidin-4,4-diyl, 1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)piperidin-4,4-diyl and 1-(cyclopropylcarbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 2; and n is an integer from 0 to 1; provided that when m is 2, then n is 0;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3R-yl, piperidin-3R-yl, and piperidin-4-yl;

a is 1;

L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—;

R³ is selected from the group consisting of methyl, 1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl and thiazol-2-yl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is

is selected from the group consisting of phenyl, pyridin-3-yl, pyridin-4-yl and pyrazol-4-yl;

and wherein

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl, tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl, imidazol-1-yl and oxetan-3-yl;

provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the binding position of the

to the

provided further that when

is pyridin-4-yl or pyrazol-4-yl, then

is bound to

at the 3-position, relative to the binding position of the

to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; n is an integer from 0 to 1; m is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

is 4-(phenyl);

and wherein

is selected from the group consisting of 4-(4-bromo-phenyl), 4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl), 4-(tetrazol-5-yl), and 3-(pyrazol-3-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl;

m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl;

a is 1;

L¹ is —C(O)—;

R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl and 1-methyl-cyclopropyl;

b is an integer from 0 to 1;

R⁴ is selected from the group consisting of 2-fluoro and 2-methyl;

R⁵ is

and wherein

is selected from the group consisting of 4-(pyridin-3-yl), 4-(pyridin-4-yl), 4-(1-methyl-pyrazol-4-yl), 4-(1-isopropyl-pyrazol-4-yl), 4-(1-cyclopropyl-pyrazol-4-yl), 4-(1-cyclobutyl-pyrazol-4-yl), 4-(1-methyl-pyrazol-5-yl), and 4-(5-methyl-oxadiazol-2-yl);

wherein

is bound to the

phenyl at the 4-position, relative to the point of attachment of the

phenyl to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

R¹ and R² are taken together to form cyclopropyl; m is an integer from 0 to 1; n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is phenyl; R⁵ is

is 4-(phenyl); and wherein

is selected from the group consisting of 4-(pyridin-3-yl) and 4-(1-methyl-pyrazol-4-yl);

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one R¹¹ group; (b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group; and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains O or NR¹⁰; provided that the O or NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl containing the O or NR¹⁰ is optionally substituted with one R¹¹ group and further optionally substituted with one R¹² group.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₆cycloalkyl; and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one R¹¹ group; (b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group; and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered, saturated heterocyclyl contains O or NR¹⁰; provided that the O or NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 6-membered, saturated heterocyclyl containing the O or NR¹⁰ is optionally substituted with one R¹¹ group and further optionally substituted with one R¹².

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₆cycloalkyl; and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains NR¹⁰; provided that the NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)piperidin-4,4-diyl, 1-(isopropyl)piperidin-4,4-diyl, 1-(ethenyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl, and 1-(methoxycarbonyl)-azetidin-3,3-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(ethenylcarbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl, and tetrahydro-pyran-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, and tetrahydro-pyran-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl, 1-(isopropylcarbonyl)-piperidin-4,4-diyl, 1-(2-hydroxyethyl)-piperidin-4,4-diyl, 1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)piperidin-4,4-diyl, and 1-(cyclopropylcarbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)piperidin-4,4-diyl, 1-(isopropyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, 1-(benzyl)piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)piperidin-4,4-diyl, and 1-(benzyl)-piperidin-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, and tetrahydropyran-4,4-diyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together to form cyclopropyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹° is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₄alkyl), —C(O)—(C₃₋₆cycloalkyl),

wherein Z¹ is selected from the group consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹° is selected from the group consisting of hydrogen, C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₂alkyl), —CH₂-(phenyl), —C(O)—(C₁₋₄alkyl), —C(O)-(cyclopropyl) and —C(O)—NR^(A)R^(B); wherein R^(A) and R^(B) are each independently selected from the group consisting of hydrogen and methyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —(C₂alkyl)-O—(C₁₋₄alkyl), —C(O)O—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl),

—C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl); wherein Z¹ is selected from the group consisting of —CH₂—, —O— and —N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxy substituted C₁₋₂alkyl), —CH₂-(phenyl), —(C₂alkyl)-O—(C₁₋₂alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl), —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(A)R^(B), —SO₂—(C₁₋₂alkyl), wherein R^(A) and R^(B) are each independently selected from the group consisting of hydrogen and methyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substituted C₁₋₂alkyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH and —C(O)O—(C₁₋₄alkyl).

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃ and hydroxy substituted C₁₋₂alkyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R¹² is selected from the group consisting of —OH, oxo, —Cl, —F, —CH₃, CF₃, —OCH₃, —OCF₃, —CH₂—OH and —CH₂CH₂—OH.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 0.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 0. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 1.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein n is 0. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein n is 1. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein n is 2.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 0 and n is 0. In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 1 and n is 1. In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 1 and n is 0 or alternatively, m is 0 and n is 1. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein m is 0 and n is 2.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein is

selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl, piperidin-3R-yl and piperidin-4-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl and piperidin-4-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein a is 1. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein a is O.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein L¹ is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR^(L)— and —SO₂—; wherein R^(L) is selected from the group consisting of hydrogen and methyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein L¹ is selected from the group consisting of —C(O)—, —C(O)—NR^(L)— and —SO₂—; wherein R^(L) is selected from the group consisting of hydrogen and methyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein L¹ is selected from the group consisting of —C(O)— and —SO₂—. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein L¹ is —C(O)—.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; wherein the C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₂alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, fluorinated C₁₋₂alkyl, C₂₋₄alkenyl, C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein the C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl is optionally substituted with a substituent selected from the group consisting of halogen, hydroxy, C₁₋₂alkyl, (C₁₋₂alkyl)-OH, fluorinated C₁₋₂alkyl, cyano and NH₂; and wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and methyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of C₂₋₄alkenyl, C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl and 5 to 6-membered heteroaryl; wherein the C₃₋₆cycloalkyl, 5 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of C₂alkenyl, C₃cycloalkyl, 5-membered, saturated heterocyclyl and 5-membered heteroaryl; wherein the C₃cycloalkyl, 5-membered, saturated heterocyclyl or 5-membered heteroaryl is optionally substituted with a substituent selected from the group consisting of halogen, C₁₋₂alkyl, fluorinated C₁₋₂alkyl and cyano.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of methyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl. 3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino, dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, and pyridin-3-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of ethyl, 1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl, 3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, oxetan-2-yl, oxetan-3yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl and dimethylamino.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl and tetrahydro-furan-2-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-methyl-cyclopropyl, pyrrolidin-1-yl and 1-methyl-pyrazol-3-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl, cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and oxetan-2-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrfuran-2S-yl and oxetan-2-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl and oxetan-2-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of methyl, 1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl and thiazol-2-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl and oxetan-2-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl and 1-methyl-cyclopropyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is selected from the group consisting of cyclopropyl and 1-methyl-cyclopropyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R³ is cyclopropyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

One skilled in the art will recognize that in the embodiments of the present invention, as described herein, the

substituent group is further substituted with —(R⁴)_(b), as herein defined.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein b is an integer from 0 to 1. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein b is 1. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein b is 1

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; provided that the R⁴ group is bound to a carbon atom. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl and C₁₋₂alkoxy.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of 2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyl and 2-methoxy. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro and 3-methyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, and 2-methyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of 2-fluoro, 2-methyl, 3-methyl and 2-methoxy. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is selected from the group consisting of 2-fluoro and 2-methyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁴ is 2-methyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is

is a 5-membered heteroaryl, and

is bound at the 3-position, relative to the point of attachment of the

to the

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is

is phenyl or a 6-membered heteroaryl, and

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is

is phenyl or a 6-membered heteroaryl, and

is bound at the 4-position, relative to the point of attachment of the

to the

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein

selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

selected from the group consisting of phenyl, heteroaryl and partially unsaturated heterocyclyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

selected from the group consisting of phenyl, naphthyl, 5 to 6-membered heteroaryl, 9 to 10-membered heteroaryl and partially unsaturated 9 to 10-membered heterocyclyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2-fluoro-4-(1-cyano-cuclopropyl)-phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl, 4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl 3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl, 3-(cyclopropylcarbonyl-amino)-phenyl, 3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl, 3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl, 3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl, 6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl, 7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl, 6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cycloprpoyl-pyridin-3-yl, 6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl, 5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)indol-5-yl, 1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl, 2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl, 2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl, 2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl, 3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl, 4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl, 2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl, 2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl, 6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl, quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl, 1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-7-methoxymethyl-indazol-4-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-7-hydroxymethyl-indazol-4-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl, 2-methyl-3-hydroxymethyl-indazol-5-yl, 2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl, 2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl, 1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl, 2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl, 1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydro-benzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, 1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl, 1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl, [1,2,4]triazo[4,3-a]pyridin-6-yl, 3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl, and 4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, 3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl, 6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl, 6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl, 2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, 2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl, and pyrrolo[2,3-b]pyridin-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indaozl-5-yl, 1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-4-yl, indol-5-yl, indol-6-yl, quinolin-5-yl, quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, benzimidazol-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, benzthiazol-5-yl, 2,3-dimethyl-benzothiophen-5-yl, 1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, and 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl, isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, indol-4-yl, indol-5-yl, indol-6-yl, quinolin-5-yl, quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, benzthiazol-5-yl, and 2,3-dimethyl-benzothiophen-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of naphtha-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl, and 1-methyl-benzimidazol-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of naphth-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl, benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzimidazol-5-yl, and 1-methyl-benzimidazol-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 4-dimethylamino-phenyl, indol-4-yl, indol-5-yl, indol-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, benzthiazol-5-yl, and 2,3-dimethyl-benzothiophen-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein wherein

is selected from the group consisting of indol-5-yl, indol-6-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl, benzofuran-5-yl, benzothien-5-yl, and 6-cyano-naphth-2-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 3-hydroxy-phenyl, indol-5-yl, indol-6-yl, isoquinolin-6-yl, indazol-4-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, and benzthiazol-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, indol-4-yl, indol-5-yl, indol-6-yl, quinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, benzofuran-5-yl, and benzthiazol-5-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I wherein

is selected from the group consisting of indol-5-yl, indol-6-yl, isoquinolin-6-yl, and benzofuran-5-yl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein c is an integer from 0 to 2.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, cyano substituted (C₁₋₄alkyl), —(C₁₋₂alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₅cycloalkyl, 1-cyano-(C₃₋₅cycloalkyl), —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—(C₃₋₅cycloalkyl), —NH—SO₂—(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, cyano-substituted C₁₋₂alkyl, —(C₁₋₂alkyl)-O—(C₁₋₂alkyl), C₁₋₄alkoxy, fluorinated C₁₋₂alkoxy, —SO₂—(C₁₋₄alkyl), —CO²H, —C(O)O—(C₁₋₂alkyl), —C(O)—(C₁₋₂alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₂alkyl), C₃₋₅cycloalkyl, 1-cyano-cyclopropyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—C(O)—(C₃₋₅cycloalkyl) and —NH—SO₂—(C₃₋₅cycloalkyl), and oxetan-3-yl; and wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁶ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, and —NR^(M)—SO₂—(C₁₋₄alkyl); wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁶ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₂alkyl, fluorinated C₁₋₂alkyl, C₁₋₂alkoxy, fluorinated C₁₋₂alkoxy, —NR^(M)R^(N), —C(O)—(C₁₋₂alkyl), —NR^(M)—C(O)H and —NR^(M)—SO₂—(C₁₋₂alkyl); and wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein

selected from the group consisting of phenyl and 5 to 6-membered heteroaryl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein wherein

is selected from the group consisting of phenyl and 6-membered, nitrogen containing heteroaryl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein wherein

is selected from the group consisting of phenyl, pyridin-3-yl, pyridin-4-yl, and pyrazol-4-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl, pyridin-3-yl and pyridin-4-yl.

another preferred embodiment In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein d is an integer from 0 to 1.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁷ is selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy and fluorinated C₁₋₄alkoxy.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl, 5 to 6-membered, saturated, nitrogen containing heterocylyl and 5 to 6-membered, nitrogen containing heteroaryl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl and 5 to 6-membered heteroaryl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of phenyl and 5 to 6-membered, nitrogen containing heteroaryl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl, 1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl, pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, and 1-(oxetan-3-yl)-pyrazol-4-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein and wherein

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl, tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl, imidazol-1-yl, and oxetan-3-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and 5-methyl-oxadiazol-2-yl.

In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, tetrazol-5-yl, and pyrazol-3-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 4-bromo-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, tetrazol-5-yl, and pyrazol-3-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and pyridin-4-yl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein

is selected from the group consisting of pyridin-3-yl and 1-methyl-pyrazol-4-yl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein e is an integer from 0 to 2. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein e is an integer from 0 to 1.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁸ is selected from the group consisting of halogen, C₁₋₄alkyl, C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), and oxetanyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) wherein each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl) and —(C₁₋₄alkyl)-NR^(T)R^(U); wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl. In another preferred embodiment, the present invention is directed to compounds of formula (I) wherein R⁸ is selected from the group consisting of halogen and C₁₋₂alkyl.

In a preferred embodiment, the present invention is directed to compounds of formula (I) selected from the group consisting of 5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-(4-(6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 5-(4-(benzo[d]thiazol-2-yl)-2-fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one, and stereoisomers, tautomers, and pharmaceutically acceptable salts thereof.

In another preferred embodiment, the present invention is directed to compounds of formula (I) selected from the group consisting of 6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; and stereoisomers, tautomers and pharmaceutically acceptable salts thereof.

In an embodiment, the present invention is directed to compounds of formula (I) wherein R¹ and R² are taken together with the carbon atom to which they are bound to form a ring structure other than tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl.

In an embodiment, the present invention is directed to compounds of formula (I) wherein (L¹)_(a) is other than —SO₂-pyrrolidin-1-yl or —SO₂-pyridin-3-yl. In another embodiment, the present invention is directed to compounds of formula (I) wherein (L¹)_(a) is other than C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ or —SO₂—CH₃.

In an embodiment, the present invention is directed to compounds of formula (I) wherein R⁵ is other than 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, 5-chloro-pyridin-3-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 2-(piperazin-1-yl)-pyridin-4-yl, 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl, 6-(morpholin-4-yl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl.

In an embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and —SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, or 1-methyl-indazol-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R^(al) and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than benzoxazol-5-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 2-oxo-3,4-dihydro-quinolin-7-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)—R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 2-(piperazin-1-yl)-pyridin-4-yl or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0, and

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 4-(1-isobutyl-pyrazol-5-yl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(4-methylphenyl)phenyl or 4-(3-chlorophenyl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1, and

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl.

In another embodiment, the present invention is directed to compounds of formula (I) as herein described, provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl.

Additional embodiments of the present invention, include those wherein the substituents selected for one or more of the variables defined herein (e.g. R¹, R², R³, R⁴, R⁵, L¹, a, b, m, n,

etc.) are independently selected to be any individual substituent or any subset of substituents selected from the complete list as defined herein.

In additional embodiments, the present invention is directed to any single compound or subset of compounds, selected from the representative compounds listed in Tables 1-4, below.

Representative compounds of formula (I) of the present invention are listed in Table 1 to 4, below. Unless otherwise noted, where a stereogenic center is present in the listed compound, the compound was prepared as a mixture of stereo-configurations. Where a stereogenic center is present, the S- and R-designations are intended to indicate that the exact stereo-configuration of the center has been determined.

As used herein, for example, as in the Tables below, the “R¹ & R² taken together” substituent group is named independent of the imidazolid-5-one core with which it forms a spiro-ring system, with the two of the spiro-bond positions denoted in the name. For example, wherein R¹ and R² are taken together with the carbon atom to which they are bound to form a spiro-ring of the following structure:

the substituent group “R¹ & R² taken together” is named/denoted as 1-(methoxy-carbonyl)-piperidin-4,4-diyl; wherein the “4,4-diyl” nomenclature indicating that the two bonds creating the spiro linkage are made through the 4-position on the piperidine portion of the spiro-ring structure.

TABLE 1 Representative Compounds of Formula (I)

ID No. R¹ & R² taken together

(L¹)_(a) R³ (R⁴)_(b)

1 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-cyano-phenyl 3R-yl 2 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl 3 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-4-yl 3R-yl 4 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl 5 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-3-yl 3R-yl 6 cyclopropyl piperidin- C(O) cyclopropyl b = 0 pyridin-3-yl 4-yl 7 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-cyano-phenyl 4-yl 8 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-yl pyrazol-5-yl 9 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-yl pyrazol-4-yl 10 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indol-5-yl 4-yl 11 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-6-yl 3R-yl 12 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl 3R-yl 13 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl pyrazol-4-yl 14 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 15 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 16 1-(methoxy- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl carbonyl)- yl piperidin- 4,4-diyl 17 1-(methoxy- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)- yl piperidin- 4,4-diyl 18 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 pyridin-2-yl 3R-yl 19 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-yl indazol-5-yl 20 cyclopropyl piperidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl 4-yl 22 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-4-yl 3R-yl 24 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 4-yl indazol-6-yl 25 cyclopropyl piperidin- C(O) cyclopropyl b = 0 isoquinolin-7-yl 4-yl 26 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzimidazol-5- 4-yl yl 27 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-6-yl 28 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-5-yl 29 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indazol-5-yl 4-yl 30 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-7-yl 3R-yl 31 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl 32 cyclopropyl piperidin- C(O) cyclopropyl b = 0 pyridin-4-yl 4-yl 33 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indol-6-yl 3R-yl 34 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-6-yl 35 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-5-yl 36 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 benzoxazol-2-yl 3R-yl 37 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzoxazol-5-yl 4-yl 38 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl indazol-6-yl 39 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl indazol-5-yl 40 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indo1-5-yl yl 41 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-cyano-phenyl yl 42 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl pyrazol-4-yl 43 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl pyrazol-5-yl 47 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3R-yl isoquinolin-6-yl 48 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-cyano-phenyl 3R-yl 49 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl yl 50 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-hydroxy- yl phenyl 51 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl yl 52 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 benzoxazol-5-yl yl 53 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-amino-4- yl hydroxy-phenyl 54 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-form-amido-4- yl hydroxy-phenyl 55 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-hydroxy- 4-yl phenyl 57 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothiazol-5- 4-yl yl 58 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl 63 1-(benzyl)- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl piperidin- 3R-yl 4,4-diyl) 64 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-hydroxy- 3R-yl phenyl 66 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-5-yl 3R-yl 67 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-5-yl 3R-yl 68 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indol-4-yl 3R-yl 69 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-7-yl 3R-yl 71 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzothiazol-5- 3R-yl yl 72 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl methyl 73 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl methyl 74 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- isoquinolin-6-yl 3R-yl methyl 75 cyclopentyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 4-yl 76 cyclopentyl piperidin- C(O) cyclopropyl b = 0 indol-5-yl 4-yl 77 cyclopentyl piperidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl 4-yl 78 cyclopentyl azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl yl 79 cyclopentyl azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl yl 80 cyclopentyl azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl yl 81 1-methyl- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl piperidin- 3R-yl 4,4-diyl 82 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 3R-yl 83 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 3-cyano-phenyl 3R-yl 84 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 3-methyl- 3R-yl sulfonyl-amino- phenyl 85 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-methoxy- 3R-yl phenyl 90 1-(benzyl)- pyrrolidin- C(O) ethenyl b = 0 benzofuran-5-yl piperidin- 3R-yl 4,4-diyl) 92 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-4-yl 3R-yl 93 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-chloro-phenyl 3R-yl methyl 94 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 2,4-dichloro- 3R-yl methyl phenyl 95 1-(benzyl)- pyrrolidin- C(O) NH₂ b = 0 benzofuran-3-yl piperidin- 3R-yl 4,4-diyl 96 1-(benzyl)- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl piperidin- 3R-yl 4,4-diyl 97 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-methyl-phenyl 4-yl 98 cyclopropyl piperidin- C(O) cyclopropyl b = 0 2-methoxy- 4-yl phenyl 99 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-methoxy- 4-yl phenyl 100 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-methyl-phenyl 3R-yl 101 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-methyl-phenyl 3R-yl 102 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-fluoro-phenyl) 3R-yl 103 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-methoxy- 3R-yl phenyl 104 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-trifluoro- 3R-yl methyl-phenyl 105 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-fluoro-phenyl) 3R-yl 106 piperidin- pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl 4,4-diyl 3R-yl 107 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-trifluoro- 4-yl methyl-phenyl 108 cyclopropyl piperidin- C(O) cyclopropyl b = 0 3-hydroxy- 4-yl phenyl 109 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 4-yl 110 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-fluoro-phenyl 4-yl 111 cyclopropyl piperidin- C(O) cyclopropyl b = 0 3-methyl-phenyl 4-yl 112 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-chloro-phenyl 3R-yl 113 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-methoxy- 3R-yl phenyl 114 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-chloro-phenyl 3R-yl 115 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-hydroxy- 3R-yl phenyl 116 cyclopentyl pyrrolidin- C(O) 1-methyl- b = 0 benzofuran-5-yl 3R-yl cycloprop- 1-yl 117 cyclopentyl pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-yl 3S-yl 1-yl 118 cyclopentyl pyrrolidin- C(O) 1-methyl- b = 0 benzofuran-5-yl 3R-yl pyrazol-3-yl 119 cyclopentyl pyrrolidin- C(O) 2,2,2- b = 0 benzofuran-5-yl 3R-yl trifluoro- ethyl 120 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl fluoro 121 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-chloro-phenyl 3R-yl fluoro 123 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-cyano-phenyl 3R-yl 124 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-dimethyl- 3R-yl amino-phenyl 125 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-trifluoro- 3R-yl methoxy-phenyl 126 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-trifluoro- 3R-yl methyl-phenyl 127 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- hydroxy- 3R-yl indazol-5-yl ethyl)- piperidin- 4,4-diyl 128 piperidin- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 4,4-diyl 3R-yl indazol-5-yl 129 1- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl- yl carbonyl)- piperidin- 4,4-diyl 130 piperidin- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl 4,4-diyl yl 131 piperidin- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- 4,4-diyl yl indazol-5-yl 132 piperidin- azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl 4,4-diyl yl 133 piperidin- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 4,4-diyl 3R-yl 134 1- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl (cyclopropyl- yl carbonyl)- piperidin- 4,4-diyl 135 1- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- (isopropyl- yl indazol-5-yl carbonyl)- piperidin- 4,4-diyl 136 1-(dimethyl- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- amino- yl indazol-5-yl methyl- carbonyl)- piepridin- 4,4-diyl 137 1- azetidin-3- C(O) cyclopropyl b = 0 isoquino1-6-yl (isopropyl- yl carbonyl)- piperidin- 4,4-diyl 138 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- carbonyl)- 3R-yl indazol-5-yl piperidin- 4,4-diyl 139 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (isopropyl- 3R-yl indazol-5-yl carbonyl)- piperidin- 4,4-diyl 140 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (cyclopropyl- 3R-yl indazol-5-yl carbonyl)- piperidin- 4,4-diyl 141 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- amino- 3R-yl indazol-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 142 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 isoquinol-6-yl amino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 143 1- pyrrolidin- C(O) cyclopropyl b = 0 isoquinol-6-yl (isopropyl- 3R-yl carbonyl)- piperidin- 4,4-diyl 144 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 isoquinol-6-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 145 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-dimethyl- 3R-yl amino-phenyl 146 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-trifluoro- 3R-yl methoxy-phenyl 147 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 148 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 149 1-(dimethyl- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl amino- yl methyl- carbonyl)- piperidin- 4,4-diyl 150 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 151 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl- 3R-yl carbonyl)- piperidin- 4,4-diyl 152 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (cyclopropyl- 3R-yl carbonyl)- piperidin- 4,4-diyl 153 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl amino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 154 1-(dimethyl- azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl amino- yl methyl- carbonyl)- piperidin- 4,4-diyl 155 piperidin pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- 4,4-diyl 3R-yl benzofuran-5-yl 156 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl methoxy 157 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indo1-5-yl 3R-yl methoxy 158 cyclopropyl piperidin- C(O) cyclopropyl b = 0 3-fluoro-phenyl 4-yl 159 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl hydroxy- 3R-yl ethyl)- piperidin- 4,4-diyl 160 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 1,2,3,4-trihydro- carbonyl)- 3R-yl 2-methyl- piperidin- carbonyl- 4,4-diyl isoquinolin-6-yl 161 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 1,2,3,4,4a,8a- carbonyl)- 3R-yl hexahydro-2- piperidin- methyl- 4,4-diyl carbonyl- isoquinolin-6-yl 162 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (isopropyl)- 3R-yl indazol-5-yl piperidin- 4,4-diyl 163 1- pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl (isopropyl)- 3R-yl piperidin- 4,4-diyl 164 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 indo1-5-yl amino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 165 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl amino- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 166 1- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl)- yl piperidin- 4,4-diyl 167 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (isopropyl)- 3R-yl piperidin- 4,4-diyl 168 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl hydroxy- 3R-yl ethyl)- piperidin- 4,4-diyl 169 1- (isopropyl)- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- piperidin- yl indazol-5-yl 4,4-diyl 170 1-(2- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- hydroxy- yl indazol-5-yl ethyl)- piperidin- 4,4-diyl 171 1- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- (cyclopropyl- 3R-yl benzofuran-5-yl carbonyl)- piperidin- 4,4-diyl 172 1- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- (isopropyl- 3R-yl benzofuran-5-yl carbonyl)- piperidin- 4,4-diyl 173 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- hydroxy- 3R-yl benzofuran-5-yl ethyl)- piperidin- 4,4-diyl 174 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- amino- 3R-yl benzofuran-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 178 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl benzofuran-5-yl 179 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl methyl benzofuran-5-yl 180 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- benzofuran-5-yl 3R-yl methyl 181 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- carbonyl)- 3R-yl benzothien-5-yl piperidin- 4,4-diyl 182 1-(dimethyl- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- amino- 3R-yl benzothien-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 183 1- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- (isopropyl- 3R-yl benzothien-5-yl carbonyl)- piperidin- 4,4-diyl 184 1- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- (isopropyl)- 3R-yl benzothien-5-yl piperidin- 4,4-diyl 185 1-(2- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl hydroxy- yl ethyl)- piperidin- 4,4-diyl 186 1- pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- (isopropyl)- 3R-yl benzofuran-5-yl piperidin- 4,4-diyl 187 1- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl (isopropyl)- yl piperidin- 4,4-diyl 188 1- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl)- yl piperidin- 4,4-diyl 189 cyclopentyl pyrrolidin- SO₂ pyrrolidin- b = 0 benzofuran-5-yl 3S-yl 1-yl 190 cyclopentyl pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl 3R-yl furan-2S-yl 191 cyclopentyl pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl 3R-yl furan-2R-yl 192 cyclopentyl pyrrolidin- C(O) 1-cyano- b = 0 benzofuran-5-yl 3R-yl cyclopropyl 193 1-(benzyl)- pyrrolidin- C(O) cyclopropyl b = 0 isoquinolin-6-yl piperidin- 3R-yl 4,4-diyl) 200 cyclopropyl pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- 3R-yl cyclopropyl indazol-5-yl 201 cyclopropyl pyrrolidin- C(O) 1-methyl- b = 0 1-methyl- 3R-yl cyclopropyl indazol-5-yl 202 cyclopropyl pyrrolidin- C(O) 1-hydroxy- b = 0 2-fluoro-4- 3R-yl cyclopropyl chloro-phenyl 203 cyclopropyl pyrrolidin- C(O) 1-hydroxy- b = 0 6-methoxy- 3R-yl cyclopropyl naphth-2-yl 204 cyclopropyl pyrrolidin- C(O) oxetan-2-yl b = 0 1-methyl- 3R-yl indazol-5-yl 205 cyclopropyl azetidin-3- C(O) tetrahydro- 2- 1-methyl- yl furan-2-yl methyl indazol-5-yl 206 cyclopropyl azetidin-3- C(O) tetrahydro- 2- 1-methyl- yl furan-2S-yl methyl indazol-5-yl 207 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 208 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclobutyl methyl indazol-5-yl 209 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-chloro-4- 3R-yl fluoro-phenyl 210 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-5-yl 3S-yl 211 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3S-yl 212 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-cynaomethyl- 3R-yl indol-5-yl 213 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl indol-5-yl 214 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-methyl-indol- 3R-yl 5-yl 215 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-indol- 3R-yl 5-yl 216 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-hydroxy- 3R-yl methyl-indol-5- yl 217 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-(2- 3R-yl hydroxyethyl)- indol-5-yl 218 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1,3-dimethyl- 3R-yl indazol-5-yl 219 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-amino- 3R-yl isoquinolin-6-yl 220 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-fluoro- 3R-yl isoquinolin-6-yl 221 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl aminocarbonyl- indazol-6-yl 222 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-cyano-naphth- yl fluoro 2-yl 223 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-fluoro-naphth- yl methyl 2-yl 224 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-cyano-naphth- yl methyl 2-yl 225 cyclopropyl azetidin-3- C(O) 1-fluoro- 2- 6-cyano-naphth- yl cyclopropyl fluoro 2-yl 226 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-cyano-naphth- yl fluoro 2-yl 227 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro indazol-6-yl 228 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-fluoro- yl fluoro quinolin-2-yl 229 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-cyano- 3R-yl fluoro quinolin-6-yl 230 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl methyl 231 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl methyl benzothien-5-yl 232 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl fluoro 233 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl fluoro 234 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl fluoro 236 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl fluoro 237 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-4-yl 3R-yl fluoro 238 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl methyl 239 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl methyl 240 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl fluoro 241 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl fluoro 242 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl fluoro benzofuran-5-yl 243 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl fluoro benzothien-5-yl 244 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl fluoro benzofuran-5-yl 245 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl fluoro benzothien-5-yl 246 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl fluoro 247 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl fluoro 248 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-6-yl 3R-yl fluoro 249 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-7-yl 3R-yl fluoro 250 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-5-yl 3R-yl fluoro 251 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzoxazol-2-yl 3R-yl fluoro 252 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzthiazol-2-yl 3R-yl fluoro 253 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-5-yl 3R-yl fluoro 254 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-cyano- 3R-yl fluoro benzofuran-5-yl 255 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-cyano- 3R-yl methyl benzofuran-5-yl 256 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-cyano- 3R-yl benzofuran-5-yl 257 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinolin-3-yl 3R-yl fluoro 258 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- quinazolin-7-yl 3R-yl fluoro 259 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 6-fluoro- 3R-yl fluoro quinolin-2-yl 260 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 8-fluoro- 3R-yl fluoro quinolin-2-yl 261 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-3-yl 3R-yl fluoro 262 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 1-methyl- 3R-yl methyl indazol-5-yl 263 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-indol- yl methyl 5-yl 264 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl chloro indazol-5-yl 265 cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 1-methyl- 3R-yl cyclopropyl methyl indazol-5-yl 266 cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 6-fluoro-naphth- 3R-yl cyclopropyl methyl 2-yl 268 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-cyano- yl fluoro benzthiazol-2-yl 269 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-cyano-naphth- yl cyclopropyl methyl 2-yl 270 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-methyl- yl fluoro benzthiazol-2-yl 271 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-fluoro- yl fluoro benzthiazol-2-yl 272 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl methyl 2-yl 273 cyclopropyl azetidin-3- C(O) 1-fluoro- 2- 6-cyano-naphth- yl cyclopropyl methyl 2-yl 274 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-chloro- yl fluoro benzthiazol-2-yl 275 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-fluoro- yl quinolin-2-yl 276 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-cyano- yl quinolin-6-yl 277 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-cyano- yl quinolin-2-yl 278 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzofuran-5-yl 3R-yl methyl 279 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl methyl 280 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl methyl benzofuran-5-yl 281 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl- 3R-yl methyl benzothien-5-yl 282 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl methyl benzofuran-5-yl 283 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2,3-dimethyl- 3R-yl methyl benzothien-5-yl 284 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl methyl 286 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-5-yl 3R-yl methyl 287 cyclopropyl azetidin-3- C(O) cyclopropyl 2- benzofuran-5-yl yl methyl 288 cyclopropyl azetidin-3- C(O) cyclopropyl 2- benzothien-5-yl yl methyl 289 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl methyl benzofuran-5-yl 290 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2,3-dimethyl- yl methyl benzothien-5-yl 291 cyclopropyl azetidin-3- C(O) cyclopropyl 2- indol-5-yl yl methyl 292 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl methyl indazol-5-yl 293 cyclopropyl azetidin-3- C(O) cyclopropyl 2- indazol-5-yl yl methyl 294 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- 3R-yl benzofuran-5-yl 295 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-methyl- 3R-yl benzothien-5-yl 296 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl benzothien-5-yl 297 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl 3R-yl 298 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benothien-5-yl 3R-yl 299 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indol-6-yl yl 300 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 indazol-4-yl yl 301 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-6-yl 3R-yl 302 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-4-yl 3R-yl 303 cyclopropyl azetidin-3- C(O) cyclopropyl 2- indol-6-yl yl methyl 304 cyclopropyl azetidin-3- C(O) cyclopropyl 2- indazol-4-yl yl methyl 305 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl methyl 306 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-4-yl 3R-yl methyl 307 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzoxazol-2-yl 3R-yl 308 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzthiazol-2-yl 3R-yl 309 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl 3R-yl 310 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-5-yl 3R-yl 311 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 6-fluoro-naphth- 3R-yl 2-yl 312 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinazolin-7-yl 3R-yl 313 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 8-fluoro-naphth- 3R-yl 2-yl 314 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indol-3-yl 3R-yl 315 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 8-fluoro- yl quinolin-7-yl 317 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl-indol- 3R-yl methyl 5-yl 318 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluoro sulfonyl-amino)- phenyl 319 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 2-methyl-indol- 3R-yl fluoro 5-yl 320 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-chloro- yl fluoro naphth-2-yl 321 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-chloro- yl cyclopropyl methyl naphth-2-yl 324 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 7-fluoro-naphth- yl fluoro 2-yl 332 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-methoxy- yl cyclopropyl methyl naphth-2-yl 334 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-methyl- yl cyclopropyl methyl naphth-2-yl 335 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-6-yl 336 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl methyl indazol-6-yl 339 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-chloro- yl quinolin-7-yl 340 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 3-chloro- yl cyclopropyl methyl quinolin-7-yl 343 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl benzimidazol-5- yl 344 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl-indol- yl 5-yl 345 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinolin-2-yl yl 346 cyclopropyl azetidin-3- C(O) cyclopropyl 2- quinolin-7-yl yl fluoro 347 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl fluoro indazol-5-yl 348 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl fluoro benzimidazol-5- yl 349 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-fluoro-naphth- yl fluoro 2-yl 350 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 8-fluoro-naphth- yl fluoro 2-yl 351 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-methoxy- yl fluoro napth-2-yl 352 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl fluoro benzothien-5-yl 353 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro benzofuran-5-yl 354 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 2-methyl- 3R-yl cyclopropyl fluoro benzothien-5-yl 355 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 2-methyl- 3R-yl cyclopropyl fluoro benzofuran-5-yl 356 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro benzothiazol-5- yl 357 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl fluoro indazol-5-yl 359 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-fluoro-naphth- yl cyclopropyl fluoro 2-yl 361 cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 1-methyl- 3R-yl cyclopropyl fluoro indazol-5-yl 363 cyclopropyl pyrrolidin- C(O) 1-methyl- 2- 6-fluoro-naphth- 3R-yl cyclopropyl fluoro 2-yl 365 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-fluoro-naphth- yl cyclopropyl fluoro 2-yl 366 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-methoxy- yl cyclopropyl fluoro naphth-2-yl 368 cyclopropyl azetidin-3- C(O) cyclopropyl 2- naphth-2-yl yl fluoro 369 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 6-fluoro-naphth- yl fluoro 2-yl 370 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 1-methyl- 3R-yl cyclopropyl fluoro indazol-5-yl 372 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- naphth-2-yl yl cyclopropyl fluoro 373 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl fluoro 2-yl 374 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 8-fluoro-naphth- yl cyclopropyl fluoro 2-yl 375 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 8-methoxy- yl cyclopropyl fluoro naphth-2-yl 377 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl fluoro benzimidazol-5- yl 378 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl fluoro benzimidazol-5- yl 380 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 8-methoxy- yl fluoro naphth-2-yl 381 cyclopropyl pyrrolidin- C(O) 1-hydroxy- 2- 6-fluoro-naphth- 3R-yl cyclopropyl fluoro 2-yl 383 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-chloro- yl cyclopropyl fluoro naphth-2-yl 384 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 7-fluoro-naphth- yl cyclopropyl fluoro 2-yl 385 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-cyano-naphth- yl cyclopropyl fluoro 2-yl 387 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl- 3R-yl fluoro benzofuran-5-yl 388 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl- 3R-yl methyl benzofuran-5-yl 389 cyclopropyl piperidin- C(O) cyclopropyl b = 0 3R-yl indazol-5-yl 391 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl methyl benzothien-5-yl 392 cyclopropyl azetidin-3- C(O) cyclopropyl 3- benzothien-5-yl yl methyl 393 cyclopropyl azetidin-3- C(O) cyclopropyl 3- benzofuran-5-yl yl methyl 394 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3R-yl 395 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3R-yl 396 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-5-yl 398 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2,3-dimethyl- yl methyl benzofuran-5-yl 399 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2,3-dimethyl- 3R-yl fluoro benzofuran-5-yl 400 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 6-amino-pyridin- 3R-yl 2-yl 401 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-methoxy- 3R-yl carbonyl-phenyl 404 cyclopropyl azetidin-3- C(O) cyclopropyl 3- benzothien-5-yl yl fluoro 405 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 1-methyl- 3R-yl fluoro indazol-5-yl 406 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2,3-dimethyl- 3R-yl fluoro benzothien-5-yl 408 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-hydroxy- 3S-yl phenyl 409 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl 410 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3S-yl indazol-5-yl 414 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- indazol-5-yl 3R-yl fluoro 415 cyclopropyl azetidin-3- C(O) cyclopropyl 3- benzofuran-5-yl yl fluoro 416 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-methyl- yl fluoro benzofuran-5-yl 417 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl fluoro benzofuran-5-yl 418 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2,3-dimethyl- yl benzothien-5-yl 431 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl 3S-yl 432 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl benzothien-5-yl 433 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-methyl- yl fluoro benzothien-5-yl 434 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl fluoro benzothien-5-yl 435 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-yl yl methyl 436 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 1-methyl- yl methyl indazol-5-yl 440 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-yl yl fluoro 441 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 1-methyl- yl fluoro indazol-5-yl 442 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-6-yl yl fluoro 443 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indazol-4-yl yl fluoro 444 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- indazol-5-yl 3R-yl methyl 445 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- indazol-4-yl 3R-yl methyl 446 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-methyl- yl methyl benzothien-5-yl 447 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl methyl benzothien-5-yl 448 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indazol-5-yl yl methyl 449 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indol-5-yl yl methyl 450 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 1-methyl- 3R-yl methyl indazol-5-yl 451 cyclopropyl azetidin-3- C(O) cyclopropyl 3- indazol-5-yl yl fluoro 452 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-amino-pyridin- 3R-yl 4-yl 453 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 isochroman-7-yl 3R-yl 454 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-isopropyl- 3R-yl indazol-5-yl 455 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-6-yl 3R-yl 456 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2,3-dihydro- 3R-yl benzo[1,4]dioxin- 6-yl 457 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-indolin-5- 3R-yl yl 460 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-cyano- yl methyl benzofuran-5-yl 461 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-indolin-5- 3R-yl yl 462 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2,3-dihydro- 3R-yl benzofuran-5-yl 463 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-cyano- 3R-yl fluoro benzofuran-5-yl 464 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 chroman-6-yl 3R-yl 465 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl cyclopropyl- indazol-5-yl 466 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-chloro- 3R-yl isoquinolin-6-yl 467 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-oxo- 3R-yl isoquinolin-6-yl 468 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methoxy- 3R-yl isoquinolin-6-yl 469 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-amino- 3R-yl isoquinolin-6-yl 470 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-methoxy- 3R-yl isoquinolin-6-yl 471 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 isochroman-6-yl 3R-yl 472 cyclopropyl azetidin-3- C(O) ethyl 2- 1-methyl- yl methyl indazol-5-yl 473 cyclopropyl azetidin-3- C(O) isopropyl 2- 1-methyl- yl methyl indazol-5-yl 474 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 quinolin-3-yl 3R-yl 475 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-cyano- yl benzofuran-5-yl 476 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-cyano- 3R-yl methyl benzofuran-5-yl 477 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2-cyano- yl fluoro benzofuran-5-yl 478 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 6-bromo- 3R-yl isoquinolin-3-yl 479 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-chloro- 3R-yl isoquinolin-6-yl 480 cyclopropyl azetidin-3- C(O) 1- 2- 1-methyl- yl hydroxymethyl- methyl indazol-5-yl cyclopropyl 481 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinoxalin-6-yl yl 483 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl amino-indazol- 6-yl 484 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl methoxymethyl- indazol-6-yl 485 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl hydroxymethyl- indazol-6-yl 486 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-7- 3R-yl methoxymethyl- indazol-4-yl 487 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-7- 3R-yl hydroxymethyl- indazol-5-yl 488 cyclopropyl azetidin-3- C(O) dimethylamino 2- 1-methyl- yl methyl indazol-5-yl 489 cyclopropyl azetidin-3- C(O) cyclobutyl 2- 1-methyl- yl methyl indazol-5-yl 490 cyclopropyl pyrrolidin- C(O) oxetan-3-yl b = 0 1-methyl- 3R-yl indazol-5-yl 491 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,4-dimethyl- yl indazol-5-yl 492 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,7-dimethyl- yl indazol-5-yl 493 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl cyano-indazol- 6-yl 494 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3-amino- 3R-yl carbonyl-phenyl 495 cyclopropyl azetidin-3- C(O) 2-hydroxy- 2- 1-methyl- yl propan-2-yl methyl indazol-5-yl 496 cyclopropyl azetidin-3- C(O) 3-methyl- 2- 1-methyl- yl oxetan-3-yl methyl indazol-5-yl 497 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 benzimidazol-2- 3R-yl yl 498 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 499 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl methyl indazol-5-yl 500 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1,2-dimethyl- 3R-yl 1,2-dihydro-3- oxo-indazol-5-yl 501 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2- yl cyclopropyl- methyl-indazol- 5-yl 502 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-fluoro- yl isoquinolin-6-yl 503 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl pyrazolol[3,4- b]pyridin-5-yl 504 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 benzisoxazol-5- yl yl 505 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-ethyl-indazol- yl 5-yl 506 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-ethyl-indazol- yl 5-yl 507 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl indazol-5-yl 508 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-isopropyl- yl indo1-5-yl 510 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl quinolin-6-yl 511 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,8- yl naphthyridin-2- yl 512 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro- quinolin-6-yl 513 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl quinolin-7-yl 515 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl- yl indazol-4-yl 518 cyclopropyl azetidin-3- C(O) thiazol-2-yl 2- 1-methyl- yl methyl indazol-5-yl 519 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinolin-3-yl yl 520 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,8-dimethyl- yl fluoro indazol-5-yl 521 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-ethyl-indazol- yl fluoro 5-yl 522 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-cyclopropyl- yl fluoro indazol-5-yl 523 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1- yl fluoro cyclopropyl- methyl-indazol- 5-yl 524 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2- yl fluoro cyclopropyl- methyl-indazol- 5-yl 525 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-isopropyl- yl fluoro indazol-5-yl 527 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-(2- yl fluoro hydroxyethyl)- indazol-5-yl 528 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 indazol-3-yl 3R-yl 529 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- indazol-3-yl 3R-yl fluoro 530 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl-3- yl hydroxymethyl- indazol-5-yl 531 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-3-yl yl 532 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-hydroxy- yl quinolin-3-yl 533 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-(2- yl cyanoethyl)- indazol-5-yl 535 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl-4- yl chloro-quinolin- 7-yl 536 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-(2- yl fluoro hydroxyethyl)- indazol-5-yl 537 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-fluoro-4- yl fluoro chloro-phenyl 538 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- benzimidazol-2- 3R-yl fluoro yl 539 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,2,4- yl triazolo[4,3- 1]pyridin-6-yl 540 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-chloro- yl quinolin-7-yl 541 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl-indol- yl 6-yl 543 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 quinazolin-7-yl yl 545 cyclopropyl azetidin-3- C(O) oxetan-2-yl 2- 1-methyl- yl methyl indazol-5-yl 546 cyclopropyl azetidin-3- C(O) 3-hydroxy- 2- 1-methyl- yl 2-methyl- methyl indazol-5-yl propan-2-yl 548 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro benzothien-5-yl 549 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-(2- yl hydroxyethyl)- indazol-5-yl 550 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-isopropyl- yl indazol-5-yl 551 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-isopropyl- yl indazol-5-yl 552 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-(2- yl hydroxyethyl)-6- fluoro-indazol-5- yl 553 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-(2- yl hydroxyethyl)-6- fluoro-indazol-5- yl 554 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-methyl- yl quinolin-7-yl 555 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-chloro-3- yl methyl-quinolin- 7-yl 556 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-(2- yl hydroxyethyl)- indazol-5-yl 557 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl-3- 3R-yl methoxy- indazol-5-yl 558 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro benzothiazol-6- yl 559 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-chloro-4- yl methyl-quinolin- 7-yl 560 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 8-fluoro- yl quinolin-2-yl 561 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl-8- yl fluoro-quinolin- 7-yl 562 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl benzothiazol-5- yl 563 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-chloro- yl quinolin-7-yl 564 cyclopropyl azetidin-3- C(O) 1-amino- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 568 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3-(2- yl fluoro hydroxyethyl)- indol-5-yl 569 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,2-dimethyl- yl fluoro indol-5-yl 570 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2,4-dimethyl- yl quinolin-7-yl 571 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl methyl carbonyl- amino)-phenyl 572 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl fluoro indazol-5-yl 573 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,3-dimethyl- yl fluoro indol-5-yl 574 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro quinolin-7-yl 575 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro quinolin-5-yl 576 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl methyl quinolin-7-yl 578 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl methyl sulfonyl-amino)- phenyl 579 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2- yl cyclopropyl methyl aminocarbonyl- quinolin-7-yl 580 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-fluoro-4- yl cyclopropyl methyl cyano-phenyl 581 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 6-isopropyloxy- yl cyclopropyl methyl napthyl-2-yl 582 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,2-dimethyl- yl methyl indol-5-yl 583 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-carboxy- yl quinolin-7-yl 584 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl chloro indazol-5-yl 585 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluoro carbonyl- amino)-phenyl 586 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl hydroxymethyl- indazol-5-yl 587 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-3- yl methyl hydroxymethyl- indazol-5-yl 588 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl methoxymethyl- indazol-5-yl 589 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-3- yl methyl methoxymethyl- indazol-5-yl 590 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl chloro-indazol- 6-yl 591 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl chloro-indazol- 5-yl 592 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 4-chloro- yl fluoro indazol-5-yl 593 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-fluoro-4-(1- yl cyclopropyl methyl cyano- cyclopropyl)- phenyl 594 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro- yl cyclopropyl methyl quinolin-7-yl 595 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 7-bromo- yl cyclopropyl methyl quinolin-2-yl 596 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro-3- yl cyclopropyl methyl methyl-quinolin- 7-yl 597 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl-4- yl cyclopropyl methyl chloro-quinolin- 7-yl 598 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl methyl indazol-4-yl 599 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-4-yl 600 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-3-yl 603 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-methyl- yl cyclopropyl methyl quinolin-5-yl 604 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-cyano- yl cyclopropyl methyl quinolin-7-yl 605 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 4-methyl-7- yl cyclopropyl methyl bromo-quinolin- 2-yl 606 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluoro chloro-indazol- 6-yl 607 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluoro chloro-indazol- 5-yl 608 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluoro methoxymethyl- indazol-5-yl 609 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluoro hydroxymethyl- indazol-5-yl 610 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-3- yl methyl cyano-indazol- 5-yl 611 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-cyano- yl quinolin-7-yl 612 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 1-methyl- yl chloro indazol-5-yl 613 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl methyl sulfonyl-amino)- phenyl 614 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl methyl carbonyl- amino)-phenyl 615 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl fluoro carbonyl- amino)-phenyl 616 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 7-cyano-naphth- yl fluoro 2-yl 617 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 7-methoxy- yl cyclopropyl fluoro naphth-2-yl 618 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 7-methoxy- yl fluoro naphth-2-yl 619 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl fluoro sulfonyl-amino)- phenyl 620 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2- yl cyclopropyl methyl trifluoromethyl- quinolin-7-yl 621 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 7-cyano-naphth- yl cyclopropyl fluoro 2-yl 622 cyclopropyl azetidin-3- C(O) 1-hydroxy- 3- 1-methyl- yl cyclopropyl chloro indazol-5-yl 624 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 2-chloro-4- yl cyclopropyl methyl methyl-quinolin- 7-yl 627 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 628 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 629 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 4-chloro- yl methyl indazol-6-yl 630 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-fluoro-5- yl fluoro trifluoromethyl- phenyl 631 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(isopropyl- yl fluoro sulfonyl)-phenyl 632 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(isopropyl- 3R-yl fluoro sulfonyl)-phenyl 633 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(methyl- 3R-yl methyl sulfonyl)-phenyl 634 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(methyl- 3R-yl fluoro sulfonyl)-phenyl 635 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-methoxy- yl fluoro naphth-2-yl 636 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(isopropyl- 3R-yl methyl sulfonyl)-phenyl 637 cyclopropyl azetidin-3- C(O) 1-fluoro- 2- 1-methyl- yl cyclopropyl fluoro indazol-5-yl 638 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-fluoro- yl fluoro benzothiazol-2- yl 639 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5,6-difluoro- yl fluoro benzothiazol-2- yl 640 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl methyl sulfonyl)-phenyl 641 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluoro thio)-phenyl 642 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl methyl thio)-phenyl 643 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-chloro- yl fluoro benzothiazol-2- yl 644 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl- yl fluoro indazol-5-yl 645 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl fluoro thio)-phenyl 646 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl methyl sulfonyl)-phenyl 647 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 3-(cyclopropyl- 3R-yl fluoro sulfonyl)-phenyl 648 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl- yl fluoro benzimidazol-2- yl 649 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 6-chloro- yl fluoro benzoxazol-2-yl 650 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl methyl thio)-phenyl 651 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3-(cyclopropyl- yl fluoro sulfonyl)-phenyl 652 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 5-cyano- yl fluoro benzothiazol-2- yl 653 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-6- yl fluoro fluoro- benzimidazol-2- yl 654 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1,2-dimethyl- yl fluoro benzimidazol-6- yl 661 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl pyran-4,4- 3R-yl diyl 662 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 quinolin-7-yl pyran-4,4- 3R-yl ethyl diyl 663 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 quinolin-7-yl pyran-4,4- 3R-yl furan-2R-yl diyl 664 tetrahydro- pyrrolidin- C(O)O methyl b = 0 quinolin-7-yl pyran-4,4- 3R-yl diyl 665 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl pyran-4,4- 3S-yl 1-yl diyl 666 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 quinolin-7-yl pyran-4,4- 3R-yl diyl 667 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 668 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl pyran-4,4- 3R-yl ethyl diyl 669 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl pyran-4,4- 3R-yl furan-2R-yl diyl 670 tetrahydro- pyrrolidin- C(O) trifluoromethyl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 671 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-yl pyran-4,4- 3S-yl 1-yl diyl 672 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 673 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- pyran-4,4- 3R-yl ethyl indazol-5-yl diyl 674 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- pyran-4,4- 3R-yl furan-2R-yl indazol-5-yl diyl 675 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 indazol-5-yl pyran-4,4- 3S-yl 1-yl 1-methyl- diyl 680 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl furan-3,3- 3R-yl diyl 681 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 quinolin-7-yl furan-3,3- 3R-yl ethyl diyl 682 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 quinolin-7-yl furan-3,3- 3R-yl furan-2R-yl diyl 683 tetrahydro- pyrrolidin- C(O)O methyl b = 0 quinolin-7-yl furan-3,3- 3S-yl diyl 684 tetrahydro- pyrrolidin- C(O) trifluoromethyl b = 0 quinolin-7-yl furan-3,3- 3R-yl diyl 685 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl furan-3,3- 3S-yl 1-yl diyl 686 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl furan-3,3- 3R-yl diyl 687 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl furan-3,3- 3R-yl ethyl diyl 688 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl furan-3,3- 3R-yl furan-2R-yl diyl 689 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-yl furan-3,3- 3S-yl 1-yl diyl 690 tetrahydro- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- furan-3,3- 3R-yl indazol-5-yl diyl 691 tetrahydro- pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- furan-3,3- 3R-yl ethyl indazol-5-yl diyl 692 tetrahydro- pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- furan-3,3- 3R-yl furan-2R-yl indazol-5-yl diyl 693 tetrahydro- pyrrolidin- C(O) pyrrolidin- b = 0 1-methyl- furan-3,3- 3S-yl 1-yl indazol-5-yl diyl 698 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 quinolin-7-yl pyran-4,4- yl diyl 699 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 quinolin-7-yl pyran-4,4- yl ethyl diyl 700 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 quinolin-7-yl pyran-4,4- yl furan-2R-yl diyl 701 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 quinolin-7-yl pyran-4,4- yl 1-yl diyl 702 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 703 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 benzofuran-5-yl pyran-4,4- yl ethyl diyl 704 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 benzofuran-5-yl pyran-4,4- yl furan-2R-yl diyl 705 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 benzofuran-5-yl pyran-4,4- yl 1-yl diyl 706 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 707 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 1-methyl- pyran-4,4- yl ethyl indazol-5-yl diyl 708 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 1-methyl- pyran-4,4- yl furan-2R-yl indazol-5-yl diyl 709 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 1-methyl- pyran-4,4- yl 1-yl indazol-5-yl diyl 714 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 quinolin-7-yl furan-3,3- yl diyl 715 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 quinolin-7-yl furan-3,3- yl ethyl diyl 716 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 quinolin-7-yl furan-3,3- yl furan-2R-yl diyl 717 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 quinolin-7-yl furan-3,3- yl 1-yl diyl 718 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 719 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 benzofuran-5-yl furan-3,3- yl ethyl diyl 720 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 benzofuran-5-yl furan-3,3- yl furan-2R-yl diyl 721 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 benzofuran-5-yl furan-3,3- yl 1-yl diyl 722 tetrahydro- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 723 tetrahydro- azetidin-3- C(O) 1-hydroxy- b = 0 1-methyl- furan-3,3- yl ethyl indazol-5-yl diyl 724 tetrahydro- azetidin-3- C(O) tetrahydro- b = 0 1-methyl- furan-3,3- yl furan-2R-yl indazol-5-yl diyl 728 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 quinolin-7-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 729 1-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 quinolin-7-yl carbonyl)- 3R-yl ethyl azetidin- 3,3-diyl 730 1-(methoxy- pyrrolidin- C(O) tetrahydro- b = 0 quinolin-7-yl carbonyl)- 3R-yl furan-2R-yl azetidin- 3,3-diyl 731 1-(methoxy- pyrrolidin- C(O) trifluoromethyl b = 0 quinolin-7-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 732 1-(methoxy- pyrrolidin- C(O) pyrrolidin- b = 0 quinolin-7-yl carbonyl)- 3S-yl 1-yl azetidin- 3,3-diyl 733 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl carbonyl)- 3R-yl azetidin- 3,3-diyl 734 1-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl carbonyl)- 3R-yl ethyl azetidin- 3,3-diyl 735 1-(methoxy- pyrrolidin- C(O) tetrahydro- b = 0 benzofuran-5-yl carbonyl)- 3R-yl furan-2R-yl azetidin- 3,3-diyl 736 1-(methoxy- pyrrolidin- C(O) pyrrolidin- b = 0 benzofuran-5-yl carbonyl)- 3S-yl 1-yl azetidin- 3,3-diyl 737 1-(methoxy- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- carbonyl)- 3R-yl indazol-5-yl azetidin- 3,3-diyl 738 1-(methoxy- pyrrolidin- C(O) 1-hydroxy- b = 0 1-methyl- carbonyl)- 3R-yl ethyl indazol-5-yl azetidin- 3,3-diyl 739 1-(methoxy- pyrrolidin- C(O) tetrahydro- b = 0 1-methyl- carbonyl)- 3R-yl furan-2R-yl indazol-5-yl azetidin- 3,3-diyl 740 1-(methoxy- pyrrolidin- C(O) pyrrolidin- b = 0 1-methyl- carbonyl)- 3S-yl 1-yl indazol-5-yl azetidin- 3,3-diyl 741 1-(ethenyl- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-6-yl carbonyl)- 3R-yl piperidin- 4,4-diyl 742 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- hydroxy- 3R-yl benzothien-5-yl ethyl)- piperidin- 4,4-diyl 743 1- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl)- 3R-yl piperidin- 4,4-diyl 744 1- piperidin- C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl)- 3R-yl pyrrolidin- 4,4-diyl 745 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl sulfonyl)- 3R-yl piperidin- 4,4-diyl 746 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl sulfonyl)- 3R-yl piperidin- 4,4-diyl 747 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 indo1-5-yl (methoxy) 3R-yl ethyl)- piperidin- 4,4-diyl 748 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl (methoxy) 3R-yl ethyl)- piperidin- 4,4-diyl 749 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (methoxy) 3R-yl ethyl)- piperidin- 4,4-diyl 750 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (methoxy) 3R-yl indazol-5-yl ethyl)- piperidin- 4,4-diyl 751 1- pyrrolidin- C(O) cyclopropyl b = 0 indo1-5-yl (trifluoro- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 752 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (trifluoro- 3R-yl indazol-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 753 1- azetidin-3- C(O) cyclopropyl b = 0 indo1-5-yl (isopropyl- yl carbonyl)- piperidin- 4,4-diyl 754 1- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl (isopropyl- yl carbonyl)- piperidin- 4,4-diyl 755 1-(2- azetidin-3- C(O) cyclopropyl b = 0 indo1-5-yl (methoxy) yl ethyl)- piperidin- 4,4-diyl 756 1-(2- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl (methoxy- yl ethyl)- piperidin- 4,4-diyl 757 1-(2- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl hydroxy- yl ethyl)- piperidin- 4,4-diyl 758 1-(2- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl hydroxy- yl ethyl)- piperidin- 4,4-diyl 760 1-(methyl- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl sulfonyl)- yl piperidin- 4,4-diyl 761 1-(methyl- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- sulfonyl)- yl indazol-5-yl piperidin- 4,4-diyl 762 1-(methyl- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl sulfonyl)- yl piperidin- 4,4-diyl 763 1-(methyl- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl sulfonyl)- yl piperidin- 4,4-diyl 764 1- azetidin-3- C(O) cyclopropyl b = 0 benzofuran-5-yl (trifluoro- yl methyl- carbonyl)- piperidin- 4,4-diyl 765 1- azetidin-3- C(O) cyclopropyl b = 0 indol-5-yl (trifluoro- yl methyl- carbonyl)- piperidin- 4,4-diyl 766 1- azetidin-3- C(O) cyclopropyl b = 0 indazol-5-yl (trifluoro yl methyl- carbonyl)- piperidin- 4,4-diyl 775 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3- yl methyl methylsulfonyl- phenyl 776 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3- yl methyl isopropylsulfonyl- phenyl 777 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3- yl fluoro methylsulfonyl- phenyl 784 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-isopropyl- yl pyridin-3-yl 787 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 3-methyl-7- yl cyclopropyl methyl bromo-quinolin- 2-yl 788 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-oxetan-3-yl- yl indazol-5-yl 789 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-oxetan-3-yl- yl fluoro indazol-5-yl 790 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl- yl quinolin-5-yl 791 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-methyl-7- yl bromo-quinolin- 2-yl 792 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-methyl-1H- yl pyrazolo[4,3- b]pyridin-5-yl 793 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-methyl- yl [1,2,4]triazolo[4, 3-a]pyridin-6-yl 794 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 5-(2-hydroxy-2- yl methyl-propyl)- pyrid-2-yl 795 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-n-propyl- yl pyridin-3-yl 796 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 797 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(2-hydroxy-2- yl methyl-propyl)- pyridin-3-yl 798 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-cyclopropyl- yl pyridin-3-yl 799 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,8- yl naphthyridin-3- yl 800 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(1-cyano- yl cyclopropyl)- pyrid-3-yl 801 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,5- yl naphthyridin-3- yl 802 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 5-chloro-pyridin- 3R-yl 3-yl 803 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-cyclopropyl- yl indazol-5-yl 804 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1- yl cyclopropylmethyl- indazol-3-yl 805 cyclopropyl azetidin-3- C(O) pyridin-3-yl 2- 1-methyl- yl methyl indazol-5-yl 807 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-isopropyl- yl indazol-5-yl 808 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-isopropyl- yl indazol-5-yl 809 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro- quinolin-7-yl 811 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-isopropyl- 3R-yl indazol-5-yl 814 cyclopropyl azetidin-3- C(O) cyclopropyl 3- 2,3-dimethyl- yl methyl benzofu-5-yl 816 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indazol-5-yl 3S-yl 817 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3S-yl 818 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl 819 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3S-yl indazol-5-yl 822 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-methyl-3,4- 3R-yl methyl dihydro-2H- pyrido[3,2- b][1,4]oxazin-7- yl 834 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl fluoro cyano-indazol- 5-yl 836 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-3- yl methyl cyano-indazol- 5-yl 837 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-(2- yl cyclopropyl fluoro hydroxyethyl)- indazol-5-yl 839 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-methyl-7- yl bromo-quinolin- 2-yl 840 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-oxo-quinolin- yl 7-yl 841 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 7-bromo- yl quinolin-2-yl 842 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2-(2- yl cyanoethyl)- indazol-5-yl 843 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indol-5-yl 3S-yl 844 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- 3R-yl indazol-5-yl 845 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indol-5-yl 3R-yl fluoro 846 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 2,3-dimethyl- yl benzofuran-5-yl 847 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2,3-dimethyl- 3R-yl benzofuran-5-yl 848 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 3- 3R-yl carboxyphenyl 849 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl- 3R-yl methyl benzothien-5-yl 850 cyclopropyl pyrrolidin- C(O) cyclopropyl 3- 2-methyl- 3R-yl fluoro benzothien-5-yl 851 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indol-5-yl 3R-yl 855 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 5-chloro-pyridin- 3R-yl methyl 3-yl 859 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4- 4-yl trifluoromethyl- phenyl 867 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 5-amino-pyridin- 3R-yl 3-yl 868 cyclopropyl azetidin-3- C(O) cyclopropyl 2- benzothiazol-2- yl fluoro yl 869 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 2-methyl-indol- yl fluoro 5-yl 870 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-methyl-indol- yl fluoro 5-yl 871 cyclopropyl pyrrolidin- C(O) cyclopropyl 2- 1-methyl- 3R-yl fluoro indazol-5-yl 872 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 6-cyano-naphth- yl cyclopropyl fluoro 2-yl 873 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl methyl 874 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indol-6-yl 3R-yl fluoro 875 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- quinolin-7-yl 3R-yl fluoro 876 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzothien-5-yl 3R-yl fluoro 877 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzimidazol-5- 3R-yl fluoro yl 878 cyclopentyl pyrrolidin- C(O) 1-hydroxy- b = 0 benzofuran-5-yl 3R-yl cyclopropyl 879 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- indazol-6-yl 3R-yl fluoro 880 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 1-methyl- 3R-yl fluoro indazol-5-yl 881 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- pyrrolo[2,3- 3R-yl fluoro b]pyridin-5-yl 883 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- benzo[1,3]dioxol- 3R-yl methyl 5-yl 884 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 2,3- 3R-yl methyl dihydrobenzo- furan-5-yl 885 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 2-oxo- 3R-yl fluoro benzimidazol-5- yl 886 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4- 3R-yl fluoro (methylcarbonyl)- phenyl 887 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 5-bromo- yl pyridin-2-yl 888 tetrahydro- azetidin-3- SO2 methyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 889 tetrahydro- pyrrolidin- C(O)O methyl b = 0 benzofuran-5-yl pyran-4,4- 3S-yl diyl 890 tetrahydro- pyrrolidin- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- 3R-yl methyl indazol-5-yl diyl 892 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3- 3R-yl indazol-5-yl diyl 895 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 quinolin-7-yl furan-3,3- yl methyl diyl 896 tetrahydro- pyrrolidin- SO₂ methyl b = 0 quinolin-7-yl furan-3,3- 3-yl diyl 897 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 benzofuran-5-yl furan-3,3- yl methyl diyl 898 tetrahydro- azetidin-3- SO₂ methyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 900 1- pyrrolidin- SO₂ methyl b = 0 quinolin-7-yl methoxy- 3S-yl carbonyl)- azetidin- 3,3-diyl 902 tetrahydro- azetidin-3- SO₂ methyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 903 tetrahydro- azetidin-3- C(O)O methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 904 tetrahydro- azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 905 tetrahydro- azetidin-3- C(O)O methyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 907 1- pyrrolidin- C(O) trifluoro- b = 0 1-methyl- methoxy- 3R-yl methyl indazol-5-yl carbonyl)- azetidin- 3,3-diyl 908 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 909 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3-yl indazol-5-yl diyl 910 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 quinolin-7-yl pyran-4,4- yl methyl diyl 912 tetrahydro- azetidin-3- SO₂ methyl b = 0 quinolin-7-yl pyran-4,4- yl diyl 913 tetrahydro- pyrrolidin- SO₂ methyl b = 0 benzofuran-5-yl pyran-4,4- 3S-yl diyl 914 tetrahydro- pyrrolidin- SO₂ methyl b = 0 benzofuran-5-yl furan-3,3- 3S-yl diyl 915 tetrahydro- pyrrolidin- C(O)O methyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 916 1- pyrrolidin- C(O)O methyl b = 0 1-methyl- methoxy- 3S-yl indazol-5-yl carbonyl)- azetidin- 3,3-diyl 917 1- pyrrolidin- SO₂ methyl b = 0 1-methyl- methoxy- 3S-yl indazol-5-yl carbonyl)- azetidin- 3,3-diyl 920 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 quinolin-7-yl furan-3,3- 3R-yl diyl 922 tetrahydro- azetidin-3- C(O)O methyl b = 0 quinolin-7-yl pyran-4,4- yl diyl 923 1- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- methoxy- 3R-yl indazol-5-yl carbonyl)- azetidin- 3,3-diyl 925 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-hydroxy- 3R-yl phenyl 926 tetrahydro- pyrrolidin- SO₂ methyl b = 0 1-methyl- pyran-4,4- 3S-yl indazol-5-yl diyl 928 tetrahydro- azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 930 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl furan-3,3- yl diyl 931 1- pyrrolidin- C(O)O methyl b = 0 benzofuran-5-yl methoxy- 3S-yl carbonyl)- azetidin- 3,3-diyl 932 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 benzofuran-5-yl furan-3,3- yl diyl 933 tetrahydro- pyrrolidin- SO₂ methyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 934 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl furan-3,3- 3-yl diyl 935 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- yl methyl indazol-5-yl diyl 937 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 1-methyl- furan-3,3- yl methyl indazol-5-yl diyl 938 tetrahydro- pyrrolidin- C(O) trifluoro- b = 0 benzofuran-5-yl furan-3,3- 3-yl methyl diyl 941 tetrahydro- azetidin-3- C(O)O methyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 942 tetrahydro- azetidin-3- SO₂ methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 944 tetrahydro- azetidin-3- SO₂ methyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 945 tetrahydro- azetidin-3- C(O) pyrrolidin- b = 0 1-methyl- furan-3,3- yl 1-yl indazol-5-yl diyl 946 1- pyrrolidin- C(O) trifluoro- b = 0 benzofuran-5-yl (methoxy 3R-yl methyl carbonyl)- azetidin- 3,3-diyl 947 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl pyran-4,4- yl diyl 949 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 951 1-isopropyl- azetidin-3- C(O) cyclopropyl b = 0 isoquinolin-6-yl piperidin- yl 4,4-diyl 952 1- azetidin-3- C(O) cyclopropyl b = 0 1- (trifluoro- yl (trifluoromethyl- methyl- carbonyl)-indol- carbonyl)- 5-yl piperidin- 4,4-diyl 953 tetrahydro- pyrrolidin- C(O)O methyl b = 0 1-methyl- pyran-4,4- 3S-yl indazol-5-yl diyl 954 tetrahydro- pyrrolidin- C(O)O methyl b = 0 benzofuran-5-yl furan-3,3- 3S-yl diyl 955 tetrahydro- pyrrolidin- C(O) trifluoro- b = 0 1-methyl- furan-3,3- 3R-yl methyl indazol-5-yl diyl 956 1- pyrrolidin- SO₂ methyl b = 0 benzofuran-5-yl (methoxy- 3S-yl carbonyl)- azetidin- 3,3-diyl 957 1- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl (methoxy- 3R-yl carbonyl)- azetidin- 3,3-diyl 958 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 959 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 960 tetrahydro- pyrrolidin- SO₂ methyl b = 0 quinolin-7-yl pyran-4,4- 3S-yl diyl 961 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 benzofuran-5-yl pyran-4,4- yl methyl diyl 962 1- pyrrolidin- C(O) thiazol-2-yl b = 0 quinolin-7-yl (methoxy- 3R-yl carbonyl)- azetidin- 3,3-diyl 963 1- pyrrolidin- C(O)O methyl b = 0 quinolin-7-yl (methoxy- 3S-yl carbonyl)- azetidin- 3,3-diyl 964 1- azetidin-3- C(O) cyclopropyl b = 0 1-methyl- (trifluoro- yl indazol-5-yl methyl- carbonyl)- piperidin- 4,4-diyl 965 tetrahydro- pyrrolidin- C(O) trifluoro- b = 0 quinolin-7-yl pyran-4,4- 3R-yl methyl diyl 966 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 indazol-5-yl hydroxyethyl)- 3R-yl piperidin- 4,4-diyl 967 1-(2- pyrrolidin- C(O) cyclopropyl b = 0 indo1-5-yl hydroxyethyl)- 3R-yl piperidin- 4,4-diyl 968 1- pyrrolidin- C(O) cyclopropyl b = 0 benzofuran-5-yl (trifluoro- 3R-yl methyl- carbonyl)- piperidin- 4,4-diyl 969 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-hydroxy- 3S-yl phenyl 970 1- pyrrolidin- C(O) cyclopropyl b = 0 1-methyl- (methyl- 3R-yl indazol-5-yl sulfonyl)- piperidin- 4,4-diyl

In Table 2 below, the

portion of the compound of formula (I) is incorporated into the compound of formula (I) (as drawn at the beginning of Table 2) and in the orientation as drawn in the Table.

TABLE 2 Representative Compounds of Formula (I)

ID No.

   

                      (R⁴)_(b)        

341 pyrrolidin-3R-yl

b = 0 indol-5-yl 342 pyrrolidin-3R-yl

b = 0 benzthiazol-5-yl 390 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 397 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 402 pyrrolidin-3R-yl

b = 0 indol-5-yl 419 pyrrolidin-3R-yl

b = 0 indazol-5-yl 420 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 421 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 422 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 423 pyrrolidin-3R-yl

b = 0 indol-5-yl 424 pyrrolidin-3R-yl

b = 0 indazol-5-yl 425 pyrrolidin-3R-yl

b = 0 benzothien-5-yl 426 pyrrolidin-3R-yl

b = 0 indol-6-yl 427 pyrrolidin-3R-yl

b = 0 indazol-4-yl 428 pyrrolidin-3R-yl

b = 0 indol-6-yl 429 pyrrolidin-3R-yl

b = 0 indazol-4-yl 430 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 437 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 438 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 439 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 458 pyrrolidin-3R-yl

b = 0 benzofuran-5-yl 459 pyrrolidin-3R-yl

b = 0 1-methyl-indazol-5-yl 971 azetidin-3-yl

b = 0 6-cyano-naphth-2-yl

TABLE 3 Representative Compounds of Formula (I)

                      ID No.                       R¹ & R² taken together

                      (L¹)_(a)                       R³                       (R⁴)_(b)        

 21 cyclopropyl piperidin-4-yl C(O) cyclopropyl b = 0 4-bromo-phenyl  23 cyclopropyl piperidin-4-yl C(O) cyclopropyl b = 0 pyridin-3-yl  56 cyclopropyl piperidin-4-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl  59 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl  60 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 pyridin-3-yl  61 cyclopropyl piperidin-4-yl C(O) cyclopropyl b = 0 pyridin-4-yl  62 cyclopropyl piperidin-4-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-5-yl  65 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl  70 cyclopentyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 3-(pyrazol-3-yl)  91 cyclopentyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 tetrazol-5-yl 122 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 pyridin-3-yl 235 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 pyridin-4-yl 267 cyclopropyl pyrrolidin-3R-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-methyl-pyrazol-4-yl 316 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl 2-methyl 1-methyl-pyrazol-4-yl 322 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 323 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 325 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-methyl 1-isopropyl-pyrazol-4-yl 326 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-methyl 1-cyclopropyl-pyrazol-4-yl 327 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-fluoro 1-isopropyl-pyrazol-4-yl 328 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-fluoro 1-cyclopropyl-pyrazol-4-yl 329 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-fluoro 1-cyclobutyl-pyrazol-4-yl 330 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-methyl 1-cyclobutyl-pyrazol-4-yl 331 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-isopropyl-pyrazol-4-yl 333 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-methyl 1-methyl-pyrazol-4-yl 337 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-cyclopropyl-pyrazol-4-yl 338 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-cyclobutyl-pyrazol-4-yl 358 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 362 cyclopropyl pyrrolidin-3R-yl C(O) 1-methyl-cyclopropyl 2-fluoro 1-methyl-pyrazol-5-yl 364 cyclopropyl pyrrolidin-3R-yl C(O) 1-methyl-cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 371 cyclopropyl pyrrolidin-3R-yl C(O) 1-hydroxy-cyclopropyl 2-fluoro 1-methyl-pyrazol-5-yl 379 cyclopropyl pyrrolidin-3R-yl C(O) 1-hydroxy-cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 382 cyclopropyl azetidin-3-yl C(O) 1-hydroxy-cyclopropyl 2-fluoro 1-methyl-pyrazol-4-yl 407 cyclopropyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-5-yl 411 cyclopropyl pyrrolidin-3S-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 412 cyclopropyl pyrrolidin-3S-yl C(O) cyclopropyl b = 0 3-chlorophenyl 413 cyclopropyl pyrrolidin-3S-yl C(O) cyclopropyl b = 0 4-methylphenyl 514 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-5-yl 516 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-isopropyl-pyrazol-4-yl 517 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 534 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 542 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-3-yl 544 cyclopropyl azetidin-3-yl C(O) cyclopropyl b = 0 1-isobutyl-pyrazol-4-yl 547 cyclopropyl azetidin-3-yl C(O) cyclopropyl 2-fluoro 1-methyl-pyrazol-3-yl 566 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-fluoro 1-methyl-pyrazol-5-yl 577 cyclopropyl azetidin-3-yl C(O) 1-hydroxy-cyclopropyl 2-fluoro 1-methyl-pyrazol-5-yl 601 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-cyclopropylmethyl- pyrazol-3-yl 602 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-(2-methylpropyl)- pyrazol-3-yl 623 cyclopropyl pyrrolidin-3R-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-methyl-pyrazol-5-yl 655 tetrahydro-pyran-4,4-diyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 656 tetrahydro-pyran-4,4-diyl pyrrolidin-3R-yl C(O) 1-hydroxy-ethyl b = 0 1-methyl-pyrazol-4-yl 657 tetrahydro-pyran-4,4-diyl pyrrolidin-3R-yl C(O) tetrahydro-furan-2R-yl b = 0 1-methyl-pyrazol-4-yl 658 tetrahydro-pyran-4,4-diyl pyrrolidin-3S-yl C(O)O methyl b = 0 1-methyl-pyrazol-4-yl 659 tetrahydro-pyran-4,4-diyl pyrrolidin-3R-yl C(O) trifluoro-methyl b = 0 1-methyl-pyrazol-4-yl 660 tetrahydro-pyran-4,4-diyl pyrrolidin-3S-yl C(O) pyrrolidin-1-yl b = 0 1-methyl-pyrazol-4-yl 676 tetrahydro-furan-3,3-diyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 677 tetrahydro-furan-3,3-diyl pyrrolidin-3R-yl C(O) 1-hydroxy-ethyl b = 0 1-methyl-pyrazol-4-yl 678 tetrahydro-furan-3,3-diyl pyrrolidin-3R-yl C(O) tetrahydro-furan-2R-yl b = 0 1-methyl-pyrazol-4-yl 679 tetrahydro-furan-3,3-diyl pyrrolidin-3S-yl C(O) pyrrolidin-1-yl b = 0 1-methyl-pyrazol-4-yl 694 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 695 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) 1-hydroxy-ethyl b = 0 1-methyl-pyrazol-4-yl 696 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) tetrahydro-furan-2R-yl b = 0 1-methyl-pyrazol-4-yl 697 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) pyrrolidin-1-yl b = 0 1-methyl-pyrazol-4-yl 710 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 711 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) 1-hydroxy-ethyl b = 0 1-methyl-pyrazol-4-yl 712 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) tetrahydro-furan-2R-yl b = 0 1-methyl-pyrazol-4-yl 713 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) pyrrolidin-1-yl b = 0 1-methyl-pyrazol-4-yl 725 1-(methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 726 1-(methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3R-yl C(O) 1-hydroxy-ethyl b = 0 1-methyl-pyrazol-4-yl 727 1-(methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3R-yl C(O) tetrahydro-furan-2R-yl b = 0 1-methyl-pyrazol-4-yl 759 piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 767 1-(isopropyl-carbonyl)-piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 768 1-(dimethyl-amino-methyl-carbonyl)- azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl piperidin-4,4-diyl 769 1-(methyl-sulfonyl)-piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 770 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 771 1-(isopropyl)-piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 772 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl azetidin-3-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 785 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-isobutyl-pyrazol-5-yl 786 cyclopropyl azetidin-3-yl C(O) 1-methyl-cyclopropyl 2-methyl 1-cyclopropylmethyl- pyrazol-5-yl 812 cyclopropyl piperidin-3S-yl C(O) cyclopropyl b = 0 4-methyl-phenyl 813 cyclopropyl piperidin-3S-yl C(O) cyclopropyl b = 0 3-chlorophenyl 815 cyclopropyl piperidin-3S-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 820 cyclopropyl piperidin-3R-yl C(O) cyclopropyl b = 0 3-chloro-phenyl 821 cyclopropyl piperidin-3R-yl C(O) cyclopropyl b = 0 4-methyl-phenyl 823 cyclopropyl piperidin-3R-yl C(O) cyclopropyl b = 0 1-methyl-pyrazol-4-yl 882 cyclopentyl pyrrolidin-3R-yl C(O) cyclopropyl 2-methyl 5-methyl-oxadiazol-2-yl 891 1-methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3S-yl SO₂ methyl b = 0 1-methyl-pyrazol-4-yl 893 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) trifluoro-methyl b = 0 1-methyl-pyrazol-4-yl 894 tetrahydro-furan-3,3-diyl pyrrolidin-3S-yl C(O)O methyl b = 0 1-methyl-pyrazol-4-yl 899 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) trifluoro-methyl b = 0 1-methyl-pyrazol-4-yl 901 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O) thiazol-2-yl b = 0 1-methyl-pyrazol-4-yl 906 1-methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3S-yl C(O)O methyl b = 0 1-methyl-pyrazol-4-yl 911 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O) thiazol-2-yl b = 0 1-methyl-pyrazol-4-yl 918 tetrahydro-pyran-4,4-diyl pyrrolidin-3S-yl SO₂ methyl b = 0 1-methyl-pyrazol-4-yl 919 1-methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3R-yl C(O) trifluoro-methyl b = 0 1-methyl-pyrazol-4-yl 921 tetrahydro-pyran-4,4-diyl azetidin-3-yl SO₂ methyl b = 0 1-methyl-pyrazol-4-yl 924 1-methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3S-yl C(O) pyrrolidin-1-yl b = 0 1-methyl-pyrazol-4-yl 927 tetrahydro-furan-3,3-diyl azetidin-3-yl C(O)O methyl b = 0 1-methyl-pyrazol-4-yl 929 1-methoxy-carbonyl)-azetidin-3,3-diyl pyrrolidin-3R-yl C(O) thiazol-2-yl b = 0 1-methyl-pyrazol-4-yl 936 tetrahydro-pyran-4,4-diyl azetidin-3-yl C(O)O methyl b = 0 1-methyl-pyrazol-4-yl 939 tetrahydro-furan-3,3-diyl pyrrolidin-3-yl SO₂ methyl b = 0 1-methyl-pyrazol-4-yl 940 tetrahydro-furan-3,3-diyl pyrrolidin-3-yl C(O) trifluoro-methyl b = 0 1-methyl-pyrazol-4-yl 943 tetrahydro-furan-3,3-diyl pyrrolidin-3-yl C(O) thiazol-2-yl b = 0 1-methyl-pyrazol-4-yl 948 tetrahydro-pyran-4,4-diyl pyrrolidin-3R-yl C(O) thiazol-2-yl b = 0 1-methyl-pyrazol-4-yl 950 tetrahydro-furan-3,3-diyl azetidin-3-yl SO₂ methyl b = 0 1-methyl-pyrazol-4-yl

TABLE 4 Representative Compounds of Formula (I)

                      ID No.                     R¹ & R² taken together

                      (R⁴) _(b)        

44 cyclopentyl pyrrolidin-3R-yl b = 0 6-(4-methyl-piperazin- 1-yl)-pyridin-3-yl 482 cyclopropyl azetidin-3-yl b = 0 6-(pyrrolidin-1-yl)- pyridin-3-yl) 509 cyclopropyl azetidin-3-yl b = 0 6-(imidazol-1-yl)- pyridin-3-yl 526 cyclopropyl azetidin-3-yl 2-fluoro 6-(imidazol-1-yl)- pyridin-3-yl 806 cyclopropyl azetidin-3-yl b = 0 6-(morpholin-4-yl)- pyridin-3-yl 828 cyclopentyl pyrrolidin-3R-yl b = 0 2-(piperazin-1-yl)- pyridin-4-yl 829 cyclopentyl pyrrolidin-3R-yl b = 0 2-(4-methylpiperazin-1- yl)-pyridin-4-yl 838 cyclopropyl azetidin-3-yl b = 0 1-(oxetan-3-yl)-pyrazol- 4-yl

In an embodiment, the present invention is directed to compounds of formula (I) as herein described provided that the compound of formula (I) is other than one or more of compounds independently selected from the group as listed in Table 5, below.

TABLE 5

ID No. R¹ & R² taken together

(L¹)_(a) R³ (R⁴)_(b) R⁵ 8 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(1-methyl- yl pyrazol-5-yl) 9 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(1-methyl- yl pyrazol-4-yl) 13 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-(1-methyl- 3R-yl pyrazol-4-yl) 32 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(pyridin-4-yl) yl 37 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(benzoxazol-5- yl yl) 42 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-(1-methyl- yl pyrazol-4-yl) 44 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 6-(4-methyl- 3R-yl piperazin-1-yl)- pyridin-3-yl 62 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(1-methyl- yl pyrazol-5-yl) phenyl 91 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 4-(tetrazol-5-yl)- 3R-yl phenyl 107 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-(4-trifluoro- yl methyl-phenyl) 160 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 4-(1,2,3,4- carbonyl)- 3R-yl trihydro-2- piperidin- methyl-carbonyl- 4,4-diyl isoquinolin-6-yl) 161 1-(methyl- pyrrolidin- C(O) cyclopropyl b = 0 4-(1,2,3,4, carbonyl)- 3R-yl 4a,8a- piperidin- hexahydro-2- 4,4-diyl methyl-carbonyl- isoquinolin-6-yl) 189 cyclopentyl pyrrolidin- SO₂ pyrrolidin- b = 0 4-(benzofuran-5- 3S-yl 1-yl yl) 776 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 3- yl methyl isopropylsulfonyl- phenyl 784 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-isopropyl- yl pyridin-3-yl 785 cyclopropyl azetidin-3- C(O) 1-methyl- 2- 4-(1-isobutyl- yl cyclopropyl methyl pyrazol-5-yl)- phenyl 788 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-oxetan-3-yl- yl indazol-5-yl 789 cyclopropyl azetidin-3- C(O) cyclopropyl 2- 1-oxetan-3-yl- yl fluoro indazol-5-yl 791 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 4-methyl-7- yl bromo-quinolin- 2-yl 793 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 3-methyl- yl [1,2,4]triazolo[4, 3-a]pyridin-6-yl 794 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 5-(2-hydroxy-2- yl methyl-propyl)- pyrid-2-yl 796 cyclopropyl azetidin-3- C(O) 1-hydroxy- 2- 1-methyl- yl cyclopropyl methyl indazol-5-yl 797 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(2-hydroxy-2- yl methyl-propyl)- pyridin-3-yl 800 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(1-cyano- yl cyclopropyl)- pyrid-3-yl 801 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1,5-naphthyridin- yl 3-yl 802 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 5-chloro-pyridin- 3R-yl 3-yl 805 cyclopropyl azetidin-3- C(O) pyridin-3-yl 2- 1-methyl- yl methyl indazol-5-yl 806 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 6-(morpholin-4- yl yl)-pyridin-3-yl 807 cyclopropyl azetidin-3- C(O) cyclopropyl b = 0 1-isopropyl- yl indazol-5-yl 809 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 2-oxo-3,4- 3R-yl dihydro-quinolin- 7-yl 812 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-(4-methyl- 3S-yl phenyl)-phenyl 813 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-(3-chloro- 3S-yl phenyl)-phenyl 815 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-(1-methyl- 3S-yl pyrazol-4-yl)- phenyl 816 cyclopropyl piperidin- C(O) cyclopropyl b = 0 indazol-5-yl 3S-yl 817 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzothien-5-yl 3S-yl 818 cyclopropyl piperidin- C(O) cyclopropyl b = 0 benzofuran-5-yl 3S-yl 819 cyclopropyl piperidin- C(O) cyclopropyl b = 0 1-methyl- 3S-yl indazol-5-yl 821 cyclopropyl piperidin- C(O) cyclopropyl b = 0 4-(4-methyl- 3R-yl phenyl)-phenyl 822 cyclopentyl pyrrolidin- C(O) cyclopropyl 2- 4-methyl-3,4- 3R-yl methyl dihydro-2H- pyrido[3,2- b][1,4]oxazin-7- yl 828 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 2-(piperazin-1- 3R-yl yl)-pyridin-4-yl 829 cyclopentyl pyrrolidin- C(O) cyclopropyl b = 0 2-(4- 3R-yl methylpiperazin- 1-yl)-pyridin-4-yl 859 cyclopropyl piperidin-4- C(O) cyclopropyl b = 0 4-trifluoromethyl- yl phenyl 888 tetrahydro- azetidin-3- SO2 methyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 891 1-methoxy- pyrrolidin- SO2 methyl b = 0 4-(1-methyl- carbonyl)- 3S-yl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 892 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3- 3R-yl indazol-5-yl diyl 893 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 4-(1-methyl- pyran-4,4- yl methyl pyrazol-4-yl)- diyl phenyl 894 tetrahydro- pyrrolidin- C(O)O methyl b = 0 4-(1-methyl- furan-3,3- 3S-yl pyrazol-4-yl)- diyl phenyl 895 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 quinolin-7-yl furan-3,3- yl methyl diyl 896 tetrahydro- pyrrolidin- SO2 methyl b = 0 quinolin-7-yl furan-3,3- 3-yl diyl 897 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 benzofuran-5-yl furan-3,3- yl methyl diyl 898 tetrahydro- azetidin-3- SO2 methyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 899 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 4-(1-methyl- furan-3,3- yl methyl pyrazol-4-yl)- diyl phenyl 900 1- pyrrolidin- SO2 methyl b = 0 quinolin-7-yl methoxy- 3S-yl carbonyl)- azetidin-3,3- diyl 901 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 4-(1-methyl- furan-3,3- yl pyrazol-4-yl)- diyl phenyl 902 tetrahydro- azetidin-3- SO2 methyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 903 tetrahydro- azetidin-3- C(O)O methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 904 tetrahydro- azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl furan-3,3- yl diyl 905 tetrahydro- azetidin-3- C(O)O methyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 906 1-methoxy- pyrrolidin- C(O)O methyl b = 0 4-(1-methyl- carbonyl)- 3S-yl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 907 1-methoxy- pyrrolidin- C(O) trifluoro- b = 0 1-methyl- carbonyl)- 3R-yl methyl indazol-5-yl azetidin-3,3- diyl 908 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 909 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 910 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 quinolin-7-yl pyran-4,4- yl methyl diyl 911 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 4-(1-methyl- pyran-4,4- yl pyrazol-4-yl)- diyl phenyl 912 tetrahydro- azetidin-3- SO2 methyl b = 0 quinolin-7-yl pyran-4,4- yl diyl 913 tetrahydro- pyrrolidin- SO2 methyl b = 0 benzofuran-5-yl pyran-4,4- 3S-yl diyl 914 tetrahydro- pyrrolidin- SO2 methyl b = 0 benzofuran-5-yl pyran-3,3- 3S-yl diyl 915 tetrahydro- pyrrolidin- C(O)O methyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 916 1-methoxy- pyrrolidin- C(O)O methyl b = 0 1-methyl- carbonyl)- 3S-yl indazol-5-yl azetidin-3,3- diyl 917 1-methoxy- pyrrolidin- SO2 methyl b = 0 1-methyl- carbonyl)- 3S-yl indazol-5-yl azetidin-3,3- diyl 918 tetrahydro- pyrrolidin- SO2 methyl b = 0 4-(1-methyl- pyran-4,4- 3S-yl pyrazol-4-yl)- diyl phenyl 919 1-methoxy- pyrrolidin- C(O) trifluoro- b = 0 4-(1-methyl- carbonyl)- 3R-yl methyl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 921 tetrahydro- azetidin-3- SO2 methyl b = 0 4-(1-methyl- pyran-4,4- yl pyrazol-4-yl)- diyl phenyl 923 1-methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- carbonyl)- 3R-yl indazol-5-yl azetidin-3,3- diyl 925 cyclopropyl pyrrolidin- C(O) cyclopropyl b = 0 4-hydroxy- 3R-yl phenyl 926 tetrahydro- pyrrolidin- SO2 methyl b = 0 1-methyl- pyran-4,4- 3S-yl indazol-5-yl diyl 927 tetrahydro- azetidin-3- C(O)O methyl b = 0 4-(1-methyl- furan-3,3- yl pyrazol-4-yl)- diyl phenyl 928 tetrahydro- azetidin-3- C(O)O methyl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 929 1-methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl- carbonyl)- 3R-yl pyrazol-4-yl)- azetidin-3,3- phenyl diyl 930 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl furan-3,3- yl diyl 932 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 benzofuran-5-yl furan-3,3- yl diyl 933 tetrahydro- pyrrolidin- SO2 methyl b = 0 1-methyl- furan-3,3- 3S-yl indazol-5-yl diyl 934 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl furan-3,3- 3-yl diyl 935 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 1-methyl- pyran-4,4- yl methyl indazol-5-yl diyl 936 tetrahydro- azetidin-3- C(O)O methyl b = 0 4-(1-methyl- pyran-4,4- yl pyrazol-4-yl)- diyl phenyl 937 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 1-methyl- furan-3,3- yl methyl indazol-5-yl diyl 939 tetrahydro- pyrrolidin- SO2 methyl b = 0 4-(1-methyl- furan-3,3- 3-yl pyrazol-4-yl)- diyl phenyl 941 tetrahydro- azetidin-3- C(O)O methyl b = 0 1-methyl- pyran-4,4- yl indazol-5-yl diyl 942 tetrahydro- azetidin-3- SO2 methyl b = 0 quinolin-7-yl furan-3,3- yl diyl 943 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl- furan-3,3- 3-yl pyrazol-4-yl)- diyl phenyl 944 tetrahydro- azetidin-3- SO2 methyl b = 0 1-methyl- furan-3,3- yl indazol-5-yl diyl 947 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 quinolin-7-yl pyran-4,4- yl diyl 948 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 4-(1-methyl- pyran-4,4- 3R-yl pyrazol-4-yl)- diyl phenyl 949 tetrahydro- azetidin-3- C(O) thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- yl diyl 950 tetrahydro- azetidin-3- SO2 methyl b = 0 4-(1-methyl- furan-3,3- yl pyrazol-4-yl)- diyl phenyl 954 tetrahydro- pyrrolidin- C(O)O methyl b = 0 benzofuran-5-yl furan-3,3- 3S-yl diyl 956 1-methoxy- pyrrolidin- SO2 methyl b = 0 benzofuran-5-yl carbonyl)- 3S-yl azetidin-3,3- diyl 957 1-methoxy- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl carbonyl)- 3R-yl azetidin-3,3- diyl 958 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 benzofuran-5-yl pyran-4,4- 3R-yl diyl 959 tetrahydro- pyrrolidin- C(O) thiazol-2-yl b = 0 1-methyl- pyran-4,4- 3R-yl indazol-5-yl diyl 960 tetrahydro- pyrrolidin- SO2 methyl b = 0 quinolin-7-yl pyran-4,4- 3S-yl diyl 961 tetrahydro- azetidin-3- C(O) trifluoro- b = 0 benzofuran-5-yl pyran-4,4- yl methyl diyl

The present invention is further directed to intermediates in the synthesis of the compounds of formula (I), as described in more detail herein. In a preferred embodiment, the present invention is directed to compounds of formula (XVIII)

wherein R¹, R², R⁴, b,

and LG² are as herein defined. In another preferred embodiment, the present invention is directed to compounds of formula (XXI)

wherein R¹, R², R⁴, b, m, n,

and LG² are as herein defined. In another preferred embodiment, the present invention is directed to compounds of formula (XXIII)

wherein R¹, R², R³, R⁴, L¹, b, m, n,

and LG² are as herein defined. In another preferred embodiment, the present invention is directed to compounds of formula (XXV)

wherein R¹, R², R⁴, R⁵, b and

are as herein defined. In another preferred embodiment, the present invention is directed to compounds of formula (XXVII)

wherein R¹, R², R⁴, R⁵, b, m, n,

are as herein defined.

DEFINITIONS

As used herein, unless otherwise noted, the term “halogen” means chloro, bromo, fluoro, and iodo. Preferably, the halogen is bromo, chloro or fluoro.

As used herein, unless otherwise noted, the term “oxo” when used to define a substituent group means an oxygen atom which is bound to a chain or ring carbon atom through a double bond (i.e. ═O).

As used herein, the term “C_(X-Y)alkyl” whether used alone or as part of a substituent group, means any straight and branched carbon chain composition of between X and Y carbon atoms. For example, “C₁₋₆alkyl” means any straight or branched carbon chain composition of between 1 and 6 carbon atoms, including, but not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, and the like.

One skilled in the art will recognize that the term “—(C_(X-Y)alkyl)-” denotes any C_(X-Y)alkyl carbon chain as herein defined, wherein said C_(X-Y)alkyl chain is divalent and is bound through two points of attachment, preferably through two terminal carbon atoms. For example, “—(C₁₋₄alkyl)-” includes, but is not limited to —CH₂—, —CH₂CH₂—, —CH(CH₃)—, —CH₂CH₂CH₂—, —CH₂CH(CH₃)—, —CH₂CH₂CH₂CH₂—, CH₂CH(CH₃)CH₂—, and the like.

As used herein, unless otherwise noted, the term “halogenated C_(X-Y)alkyl” means any C_(X-Y)alkyl group as defined above substituted with at least one halogen atom, preferably at least one fluoro atom. For example, “halogenated C₁₋₄alkyl” includes, but is not limited to, —CF₃, —CCl₃, —CH₂I, —CH₂Br, —CH₂—CF₃, —CH₂—CCl₃, —CF₂—CF₂—CF₂—CF₃, and the like. Similarly, as used herein, unless otherwise noted, the term “fluorinated C_(X-Y)alkyl” means any C_(X-Y)alkyl group as defined above substituted with at least one fluoro atom. For example, the term “fluorinated C₁₋₄alkyl” includes, but is not limited to —CF₃, —CH₂—CF₃, —CF₂—CF₂—CF₂—CF₃, and the like.

As used herein, unless otherwise noted, the term “hydroxy substituted C_(X-Y)alkyl” means C_(X-Y)alkyl group as defined above substituted with at least one hydroxy group. Preferably, the C_(X-Y)alkyl group is substituted with one hydroxy group. Preferably, the C_(X-Y)alkyl group is substituted with a hydroxy group at the terminal carbon. For example, the term “hydroxy substituted C₁₋₄alkyl” includes, but is not limited to, —CH₂(OH), —CH₂—CH₂(OH), —CH₂—CH(OH)—CH₂, and the like.

As used herein, the term “C_(X-Y)alkenyl” whether used alone or as part of a substituent group, means any straight and branched carbon chain composition of between X and Y carbon atoms comprising at least one unsaturated double bond. For example, “C₂₋₄alkyl” means any straight or branched carbon chain composition of between 2 and 4 carbon atoms, comprising at least one double bond. Suitably examples include, but are not limited to, —CH═CH₂, —CH₂—CH═CH₂, —CH═CH₂—CH₃, —CH₂—CH₂—CH═CH₂, —CH₂—CH═CH—CH₃, and the like.

As used herein, unless otherwise noted, “C_(X-Y)alkoxy” wherein X and Y are integers, denotes an oxygen ether radical of the above described straight or branched chain C_(X-Y)alkyl groups. For example, the term “C₁₋₄alkoxy” includes, but is not limited to methoxy, ethoxy, n-propoxy, sec-butoxy, t-butoxy, n-hexyloxy and the like.

As used herein, unless otherwise noted, the term “halogenated C_(X-Y)alkoxy” wherein X and Y are integers means any oxygen ether radical as defined above substituted with at least one halogen atom, preferably at least one fluoro atom. For example, the term “halogenated C₁₋₄alkoxy” includes, but is not limited to, —OCF₃, —OCCl₃, —OCH₂I, —OCH₂Br, —OCH₂—CF₃, —OCH₂—CCl₃, —OF₂—CF₂—CF₂—CF₃, and the like. Similarly, as used herein, unless otherwise noted, the term “fluorinated C_(X-Y)alkoxy” means any oxygen ether radical as defined above substituted with at least one fluoro atom. For example, the term “fluorinated C₁₋₄alkoxy” includes, but is not limited to —OCF₃, —OCH₂—CF₃, —OCF₂—CF₂—CF₂—CF₃, and the like.

As used herein, unless otherwise noted, the term “C_(X-Y)cycloalkyl” wherein X and Y are integers means any stable saturated ring system comprising between X and Y carbon ring atoms. For example, the term “C₁₋₈cycloalkyl” means any stable 3 to 8-membered saturated ring structure, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

As used herein, unless otherwise noted, the term “benzo-fused C_(X-Y)cycloalkyl” wherein X and Y are integers, means any stable monocyclic, saturated ring structure comprising between X and Y carbon ring atoms, which saturated ring structure is benzo-fused. Suitable examples include 2,3-dihydro-1H-indenyl and 1,2,3,4-tetrahydro-naphthyl.

As used herein, unless otherwise noted, “aryl” means any carbocylic aromatic ring structure as phenyl, naphthyl, and the like. Preferably, the aryl is phenyl or naphthyl, more preferably phenyl.

As used herein, unless otherwise noted, “heteroaryl” denotes any five or six-membered monocyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to three additional heteroatoms independently selected from the group consisting of O, N and S; or any nine or ten -membered bicyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to four additional heteroatoms independently selected from the group consisting of O, N and S; and wherein the heteroaryl contains one of more S heteroatom(s), said S heteroatom(s) are each independently optionally substituted with one to two oxo groups. The heteroaryl group may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure.

Examples of suitable heteroaryl groups include, but are not limited to, pyrrolyl, furyl, thienyl, oxazolyl, imidazolyl, purazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furazanyl, indolizinyl, indolyl, isoindolinyl, indazolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, isothiazolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[4,3-b]pyridinyl, [1,2,4]triazo[4,3-a]pyridinyl, and the like.

As used herein, unless otherwise noted, the term “5 to 6-membered heteroaryl” denotes any five or six-membered monocyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to three additional heteroatoms independently selected from the group consisting of O, N and S; wherein the 5 to 6-membered heteroaryl contains one of more S heteroatom(s), said S heteroatom(s) are each independently optionally substituted with one to two oxo groups. The 5 to 6-membered heteroaryl may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure. Suitable examples include, but are not limited to, pyrrolyl, furyl, thienyl, oxazolyl, thiazolyl, imidazolyl, purazolyl, isoxazolyl, isothiazolyl, triazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furazanyl, and the like. Preferred 5 to 6-membered heteroaryl include one or more selected from the group consisting of pyrrolyl, furanyl, thienyl, oxazolyl, thiazolyl, imidazolyl, pyrazoly, triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyrazonyl, and pyranyl.

As used herein, unless otherwise noted, the term “6-membered, nitrogen containing heteroaryl” denotes any six-membered monocyclic aromatic ring structure containing at least one N heteroatom, optionally containing one to three additional heteroatoms independently selected from the group consisting of O and N. The 6-membered heteroaryl may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure. Suitable examples include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyranyl, furazanyl, and the like.

As used herein, unless otherwise noted, the term “9 to 10-membered heteroaryl” denotes any nine or ten-membered bicyclic aromatic ring structure containing at least one heteroatom selected from the group consisting of 0, N and S, optionally containing one to four additional heteroatoms independently selected from the group consisting of O, N and S; wherein the 9 to 10-membered heteroaryl contains one of more S heteroatom(s), said S heteroatom(s) are each independently optionally substituted with one to two oxo groups. The 9 to 10-membered heteroaryl may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure. Suitable examples include, but are not limited to, indolizinyl, indolyl, isoindolinyl, indazolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, isothiazolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, pyrrolo[2,3-b]pyridinyl, pyrazolo[4,3-b]pyridinyl, [1,2,4]triazo[4,3-a]pyridinyl, and the like.

As used herein, the term “heterocyclyl” denotes any four to eight-membered monocyclic, saturated or partially unsaturated ring structure containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to three additional heteroatoms independently selected from the group consisting of O, N and S; or a nine to ten -membered saturated, partially unsaturated or partially aromatic (e.g. benzo-fused) bicyclic ring system containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to four additional heteroatoms independently selected from the group consisting of O, N and S; and wherein the heterocyclyl contains one of more S heteroatom(s), said S heteroatom(s) are each independently optionally substituted with one to two oxo groups. The heterocyclyl group may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure.

Suitably examples include, but are not limited to, pyrrolinyl, pyrrolidinyl, dioxolanyl, imidazolinyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, piperazinyl, trithianyl, azepanyl, 1,4-diazepanyl, 1,4-oxazepanyl, indolinyl, isoindolinyl, chromenyl, 3,4-methylenedioxyphenyl, 2,3-dihydrobenzofuranyl, tetrahydro-furanyl, and the like. Preferred heterocycloalkyl groups include one or more selected from the group consisting of pyrrolidinyl, dioxaklanyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, 1,4-diazepanyl, 1,4-oxazepanyl, indolinyl, 2,3-dihydro-furanyl and tetrahydro-furanyl.

As used herein, unless otherwise noted, the term “5 to 6-membered saturated heterocyclyl” denotes any 5 to 6-membered monocyclic, saturated ring structure containing at least one heteroatom selected from the group consisting of O, S and N, optionally containing one to three additional heteroatoms independently selected from the group consisting of O, S and N; and wherein the 5 to 6-membered saturated heterocyclyl contains one or more S heteroatom(s), said S heteroatom(s) are each independently, optionally substituted with one to two oxo groups. The 5 to 6-membered saturated heterocyclyl group may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure. Suitable examples include, but are not limited to Suitably examples include, but are not limited to, pyrrolidinyl, dioxolanyl, imidazolidinyl, pyrazolidinyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl, thiomorpholinyl, piperazinyl, azepanyl, 1,4-diazepanyl, 1,4-oxazapanyl, and the like. Preferably, the 5 to 6-membered saturated heterocyclyl include one or more selected from the group consisting of pyrrolidinyl, dioxolanyl, piperidinyl, 1,4-dioxanyl, morpholinyl, piperazinyl, azepanyl, 1,4-diazepanyl and 1,4-oxazapanyl.

As used herein, unless otherwise noted, the term “partially unsaturated heteroaryl” denotes any five to seven-membered monocyclic partially unsaturated ring structure containing at least one unsaturated (e.g. double) bond and further containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to three additional heteroatoms independently selected from the group consisting of O, N and S; or a nine to eleven-membered partially unsaturated or partially aromatic (e.g. benzo-fused) bicyclic ring system containing at least one unsaturated (e.g. double) bond and further containing at least one heteroatom selected from the group consisting of O, N and S, optionally containing one to four additional heteroatoms independently selected from the group consisting of O, N and S; and wherein the partially unsaturated heterocyclyl contains one of more S heteroatom(s), said S heteroatom(s) are each independently optionally substituted with one to two oxo groups. The partially unsaturated heterocyclyl may be attached at any heteroatom or carbon atom of the ring such that the result is a stable structure. Suitably examples include, but are not limited to, indolinyl, isoindolinyl, 2,3-dihydrobenzofuranyl, 1,3-dihydroisobenzofuranyl, 2,3-dihydrobenzo[b]thienyl, 1,3-dihydrobenzo[c]thienyl, chromanyl, isochromanyl, 3,4-dihydro-quinolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydro-isoquinolinyl, 1,2,3,4,4a,8a-hexahydro-isoquinolinyl, 1,2-dihydro-indazolyl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl, and the like.

When a particular group is “substituted” (e.g., C_(X-Y)alkyl, C_(X-Y)cycloalkyl, aryl, heteroaryl, heterocyclyl, etc.) that group may have one or more substituents, preferably from one to five substituents, more preferably from one to three substituents, most preferably from one to two substituents, independently selected from the list of substituents.

With reference to substituents, the term “independently” means that when more than one of such substituents is possible, such substituents may be the same or different from each other.

As used herein, the notation “*” denotes the presence of a stereogenic center.

Where the compounds according to this invention have at least one chiral center, they may accordingly exist as enantiomers. Where the compounds possess two or more chiral centers, they may additionally exist as diastereomers. It is to be understood that all such isomers and mixtures thereof are encompassed within the scope of the present invention. Preferably, when the compound is present as an enantiomer, the enantiomer is present at an enantiomeric excess of greater than or equal to about 80%, more preferably, at an enantiomeric excess of greater than or equal to about 90%, more preferably still, at an enantiomeric excess of greater than or equal to about 95%, more preferably still, at an enantiomeric excess of greater than or equal to about 98%, most preferably, at an enantiomeric excess of greater than or equal to about 99%. Similarly, when the compound is present as a diastereomer, the diastereomer is present at an diastereomeric excess of greater than or equal to about 80%, more preferably, at an diastereomeric excess of greater than or equal to about 90%, more preferably still, at an diastereomeric excess of greater than or equal to about 95%, more preferably still, at an diastereomeric excess of greater than or equal to about 98%, most preferably, at an diastereomeric excess of greater than or equal to about 99%.

Furthermore, some of the crystalline forms for the compounds of the present invention may exist as polymorphs and as such are intended to be included in the present invention. In addition, some of the compounds of the present invention may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be encompassed within the scope of this invention.

Furthermore, it is intended that within the scope of the present invention, any element, in particular when mentioned in relation to a compound of formula (I), shall comprise all isotopes and isotopic mixtures of said element, either naturally occurring or synthetically produced, either with natural abundance or in an isotopically enriched form. For example, a reference to hydrogen includes within its scope ¹H, ²H (D), and ³H (T). Similarly, references to carbon and oxygen include within their scope respectively ¹²C, ¹³C and ¹⁴C and ¹⁶O and ¹⁸O. The isotopes may be radioactive or non-radioactive. Radiolabelled compounds of formula (I) may comprise a radioactive isotope selected from the group of ³H, ¹¹C, ¹⁸F, ¹²²I, ¹²³I, ¹²⁵I, ¹³¹I, ⁷⁵Br, ⁷⁶Br, ⁷⁷Br and ⁸²Br. Preferably, the radioactive isotope is selected from the group of ³H, ¹¹C and ¹⁸F.

Unless otherwise denoted through use of a “-” symbol, under standard nomenclature used throughout this disclosure, the terminal portion of the designated side chain is described first, followed by the adjacent functionality toward the point of attachment. Thus, for example, a “phenylC₁-C₆alkylaminocarbonylC₁-C₆alkyl” substituent refers to a group of the formula

Abbreviations used in the specification, particularly the Schemes and Examples, are as follows:

-   AcOH or HOAc=Acetic acid -   Boc or BOC=tert-Butoxycarbonyl -   BSA=Bovine Serum Albumin -   Cbz=Carboxybenzyl -   CDI=Carbonyldiimidazole -   CoA=Acetyl coenzyme-A -   Cu(OAc)₂=Copper Acetate -   DCE=Dichloroethane -   DCM=Dichloromethane -   DIPEA or DIEA=Diisopropylethylamine -   DMAP=4-N,N-Dimethylaminopyridine -   DME=Dimethyl Ether -   DMF=N,N-Dimethylformamide -   DMP or     Dess-Martin=1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-Periodinane     3(1H)-one -   DMSO=Dimethylsulfoxide -   DTT=Dithiothreitol -   EDAC or EDCI=1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide -   EDTA=Ethylenediaminetetraacetic acid -   Et₃N or TEA=Triethylamine -   Et₂O=Diethyl ether -   EtOAc=Ethyl acetate -   FASN=Fatty Acid Synthase -   FBS Fetal Bovine Serum -   HATU=o-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium     hexafluorophosphate -   HBTU=2-(1H-Benzotriazole-1-yl)-1,1,3,3-Tetramethyluronium     hexafluorophosphate -   hFASN=Human fatty Acid Synthase -   HOBT or HOBt=1-Hydroxybenzotriazole -   HPLC=High Performance Liquid Chromatography -   LHMDS=Lithium Bis(trimethylsilyl)amide -   MeCN=Acetonitrile -   MeOH=Methanol -   MEM=Eagle's minimum essential medium -   Mesylate=Methanesulfonate -   Mesyl=Methanesulfonyl -   MOM=Methoxymethyl -   MS-Cl=Mesyl Chloride -   MTBE=Methyl tert-Butyl Ether -   MTT=Methyl Thiazolyl Tetrazolium -   NADPH Nicotinamide adenine dinucleotide phosphate -   NMP=1-Methyl-2-pyrrolidinone -   PBS=Phosphate-buffered Saline -   Pd/C=Palladium on Carbon Catalyst -   Pd₂(OAc)₂=Palladium(II)acetate -   Pd₂(dba)₂=Bis(dibenzylidene acetone)dipalladium(0) -   Pd(dppf)=Palladium diphenylphosphinoferrocene -   Pd(PPh₃)₄=Tetrakistriphenylphosphine palladium (0) -   PPh₃=Triphenylphosphine -   RT or rt=Room temperature -   t-BOC or Boc=Tert-Butoxycarbonyl -   t-BuOK=Potassium tert-Butoxide -   TEA=Triethylamine -   TFA=Trifluoroacetic Acid -   THF=Tetrahydro-furan -   THP Tetrahydro-pyranyl -   TMOF=Trimethylorthoformate -   TMS=Trimethylsilyl -   TMS-Cl=Trimethylsilyl chloride -   Tosylate=p-Toluenesulfonate -   Tosyl=p-Toluenesulfonyl -   Triflate or OTf=Trifluoromethanesulfonate -   Triflyl=Trifluoromethanesulfonyl

As used herein, unless otherwise noted, the term “isolated form” means that the compound is present in a form which is separate from any solid mixture with another compound(s), solvent system, or biological environment. In an embodiment of the present invention, the compound of formula (I) is present in an isolated form.

As used herein, unless otherwise noted, the term “substantially pure form” means that the mole percent of impurities in the isolated compound is less than about 5 mole percent, preferably less than about 2 mole percent, more preferably, less than about 0.5 mole percent, most preferably, less than about 0.1 mole percent. In an embodiment of the present invention, the compound of formula (I) is present as a substantially pure form.

As used herein, unless otherwise noted, the term “substantially free of a corresponding salt form(s)” when used to described the compound of formula (I) means that mole percent of the corresponding salt form(s) in the isolated base of formula (I) is less than about 5 mole percent, preferably less than about 2 mole percent, more preferably, less than about 0.5 mole percent, most preferably less than about 0.1 mole percent. In an embodiment of the present invention, the compound of formula (I) is present in a form which is substantially free of corresponding salt form(s).

As used herein, unless otherwise noted, the terms “treating”, “treatment” and the like, include the management and care of a subject or patient (preferably mammal, more preferably human) for the purpose of combating a disease, condition, or disorder and includes the administration of a compound of the present invention to prevent the onset of the symptoms or complications, alleviate the symptoms or complications, or eliminate the disease, condition, or disorder.

As used herein, unless otherwise noted, the term “prevention” includes (a) reduction in the frequency of one or more symptoms; (b) reduction in the severity of one or more symptoms; (c) the delay or avoidance of the development of additional symptoms; (d) delay or avoidance of the development of the disorder or condition; and/or (f) the delay or avoidance of the progression of the disorder or condition.

One skilled in the art will recognize that when the present invention is directed to methods of prevention, a subject in need of thereof (i.e. a subject in need of prevention) includes any subject or patient (preferably a mammal, more preferably a human) who has experienced or exhibited at least one symptom of the disorder, disease, or condition to be prevented. Further, a subject in need thereof may additionally be a subject (preferably a mammal, more preferably a human) who has not exhibited any symptoms of the disorder, disease, or condition to be prevented, but who has been deemed by a physician, clinician, or other medical profession to be at risk of developing such disorder, disease, or condition. For example, the subject may be deemed at risk of developing a disorder, disease, or condition (and therefore in need of prevention or preventive treatment) as a consequence of the subject's medical history, including, but not limited to, family history, pre-disposition, co-existing (comorbid) disorders or conditions, genetic testing, and the like.

The term “subject” as used herein, refers to an animal, preferably a mammal, most preferably a human, who has been the object of treatment, observation or experiment. Preferably, the subject has experienced and/or exhibited at least one symptom of the disease or disorder to be treated and/or prevented.

The term “therapeutically effective amount” as used herein, means an amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal, or human that is being sought by a researcher, veterinarian, medical doctor, or other clinician, which response includes alleviation of the symptoms of the disease or disorder being treated.

As used herein, the term “composition” is encompasses a product comprising, consisting of and/or consisting essentially of the specified ingredients in the specified amounts, as well as any product that results, directly or indirectly, from combinations of the specified ingredients in the specified amounts.

As more extensively provided in this written description, terms such as “reacting” and “reacted” are used herein in reference to a chemical entity that is any one of: (a) the actually recited form of such chemical entity and (b) any of the forms of such chemical entity in the medium in which the compound is being considered when named.

One skilled in the art will recognize that, where not otherwise specified, the reaction step(s) is performed under suitable conditions, according to known methods, to provide the desired product. One skilled in the art will further recognize that, in the specification and claims as presented herein, when a reagent or reagent class/type (e.g., base, solvent, etc.) is recited in more than one step of a process, the individual reagents are independently selected for each reaction step and may be the same of different from each other. For example when two steps of a process recite an organic or inorganic base as a reagent, the organic or inorganic base selected for the first step may be the same or different than the organic or inorganic base of the second step. Further, one skilled in the art will recognize that when a reaction step of the present invention may be carried out in a variety of solvents or solvent systems, said reaction step may also be carried out in a mixture of the suitable solvents or solvent systems.

To provide a more concise description, some of the quantitative expressions given herein are not qualified with the term “about”. It is understood that whether the term “about” is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including approximations due to the experimental and/or measurement conditions for such given value.

To provide a more concise description, some of the quantitative expressions herein are recited as a range from about amount X to about amount Y. It is understood that when a range is recited, the range is not limited to the recited upper and lower bounds, but rather includes the full range from about amount X through about amount Y, or any amount or range therein.

Examples of suitable solvents, bases, reaction temperatures, and other reaction parameters and components are provided in the detailed descriptions which follow herein. One skilled in the art will recognize that the listing of said examples is not intended, and should not be construed, as limiting in any way the invention set forth in the claims which follow thereafter. One skilled in the art will further recognize that when a reaction step of the present invention may be carried out in a variety of solvents or solvent systems, such reaction step may also be carried out in a mixture of the suitable solvents or solvent systems.

As used herein, unless otherwise noted, the term “aprotic solvent” means any solvent that does not yield a proton. Suitable examples include, but are not limited to DMF, 1,4-dioxane, THF, acetonitrile, pyridine, dichloroethane, dichloromethane, MTBE, toluene, acetone, and the like.

As used herein, unless otherwise noted, the term “leaving group” means a charged or uncharged atom or group which departs during a substitution or displacement reaction. Suitable examples include, but are not limited to, Br, Cl, I, mesylate, tosylate, triflate, and the like.

During any of the processes for preparation of the compounds of the present invention, it may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules concerned. This may be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, ed. J.F.W. McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991. The protecting groups may be removed at a convenient subsequent stage using methods known from the art.

As used herein, unless otherwise noted, the term “nitrogen protecting group” means a group which may be attached to a nitrogen atom to protect said nitrogen atom from participating in a reaction and which may be readily removed following the reaction. Suitable nitrogen protecting groups include, but are not limited to carbamates—groups of the formula —C(O)O—R wherein R is for example methyl, ethyl, t-butyl, benzyl, phenylethyl, CH₂=CH—CH₂—, and the like; amides—groups of the formula —C(O)—R′ wherein R′ is for example methyl, phenyl, trifluoromethyl, and the like; N-sulfonyl derivatives—groups of the formula —SO₂—R″ wherein R″ is for example tolyl, phenyl, trifluoromethyl, 2,2,5,7,8-pentamethylchroman-6-yl-, 2,3,6-trimethyl-4-methoxybenzene, and the like. Other suitable nitrogen protecting groups may be found in texts such as T. W. Greene & P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991.

As used herein, unless otherwise noted, the term “oxygen protecting group” means a group which may be attached to an oxygen atom to protect such oxygen atom from participating in a reaction and which may be readily removed following the reaction. Suitable oxygen protecting groups include, but are not limited to, acetyl, benzoyl, t-butyl-dimethylsilyl, trimethylsilyl (TMS), methoxymethyl (MOM), tetrahydro-pyranyl (THP), and the like. Other suitable oxygen protecting groups may be found in texts such as T. W. Greene & P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991.

Where the processes for the preparation of the compounds according to the invention give rise to mixture of stereoisomers, these isomers may be separated by conventional techniques such as preparative chromatography.

The compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution. The compounds may, for example, be resolved into their component enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid, such as, (−)-di-p-toluoyl-D-tartaric acid and/or (+)-di-p-toluoyl-L-tartaric acid followed by fractional crystallization and regeneration of the free base. The compounds may also be resolved by formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds may be resolved using a chiral HPLC column.

Additionally, chiral HPLC against a standard may be used to determine percent enantiomeric excess (% ee). The enantiomeric excess may be calculated as follows

[(Rmoles−Smoles)/(Rmoles+Smoles)]×100%

where Rmoles and Smoles are the R and S mole fractions in the mixture such that Rmoles+Smoles=1. The enantiomeric excess may alternatively be calculated from the specific rotations of the desired enantiomer and the prepared mixture as follows:

ee=([α-obs]/[α-max])×100.

The present invention includes within its scope prodrugs of the compounds of this invention. In general, such prodrugs will be functional derivatives of the compounds which are readily convertible in vivo into the required compound. Thus, in the methods of treatment of the present invention, the term “administering” encompasses the treatment of the various disorders described with the compound specifically disclosed or with a compound that may not be specifically disclosed, but converts to the specified compound in vivo after administration to the patient. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in Design of Prodrugs, ed. H. Bundgaard, Elsevier, 1985.

For use in medicine, the salts of the compounds of this invention refer to non-toxic “pharmaceutically acceptable salts.” Other salts may, however, be useful in the preparation of compounds according to this invention or of their pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of the compounds include acid addition salts that may, for example, be formed by mixing a solution of the compound with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, sulfuric acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, citric acid, tartaric acid, carbonic acid, or phosphoric acid. Furthermore, where the compounds of the invention carry an acidic moiety, suitable pharmaceutically acceptable salts thereof may include alkali metal salts, e.g., sodium or potassium salts; alkaline earth metal salts, e.g., calcium or magnesium salts; and salts formed with suitable organic ligands, e.g., quaternary ammonium salts. Thus, representative pharmaceutically acceptable salts include, but are not limited to, the following: acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, oleate, pamoate (embonate), palmitate, pantothenate, phosphate/diphosphate, polygalacturonate, salicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, teoclate, tosylate, triethiodide, and valerate.

Representative acids that may be used in the preparation of pharmaceutically acceptable salts include, but are not limited to, the following: acids including acetic acid, 2,2-dichloroacetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, D-gluconic acid, D-glucoronic acid, L-glutamic acid, α-oxo-glutaric acid, glycolic acid, hipuric acid, hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, maleic acid, (−)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinc acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, L-pyroglutamic acid, salicylic acid, 4-amino-salicylic acid, sebaic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, thiocyanic acid, p-toluenesulfonic acid, and undecylenic acid.

Representative bases which may be used in the preparation of pharmaceutically acceptable salts include, but are not limited to, the following: bases including ammonia, L-arginine, benethamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)-ethanol, ethanolamine, ethylenediamine, N-methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2-hydroxyethyl)-morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)-pyrrolidine, secondary amine, sodium hydroxide, triethanolamine, tromethamine, and zinc hydroxide.

GENERAL SYNTHETIC SCHEMES

Compounds of formula (I) may be prepared according to the process outlined in Scheme 1, below.

Accordingly, a suitably substituted compound of formula (X), a known compound or compound prepared by known methods, is reacted with NH₃ or with a suitably substituted compound of formula (XII), wherein PG¹ is a suitably selected nitrogen protecting group such as Boc, Cbz, benzyl, 1-phenethyl, and the like; in the presence of a suitably selected source of cyanide, such as KCN, NaCN, TMS-CN, and the like; in a suitably selected solvent or mixture of solvents such as methanol, ethanol, water, and the like; to yield the corresponding compound of formula (XIII), wherein Q′ is hydrogen or PG¹, respectively.

Alternatively, a suitably substituted compound of formula (XI), wherein A¹ is C₁₋₂alkyl, a known compound or compound prepared by known methods, is reacted with NH₃ or a suitably substituted compound of formula (XII), wherein PG¹ is a suitably selected nitrogen protecting group such as Boc, Cbz, benzyl, 1-phenylethyl, and the like; in the presence of a suitably selected source of cyanide, such as TMS-CN, and the like; in a suitably selected solvent or mixture of solvents such as glacial HOAc, and the like; to yield the corresponding compound of formula (XIII), wherein Q¹ is hydrogen or PG¹, respectively.

The compound of formula (XIII) is reacted to yield the corresponding compound of formula (XV), through a one-step or two step reaction.

Where the compound of formula (XIII) Q¹ is hydrogen, the compound of formula (XIII) is reacted with hydrogen peroxide, in the presence of a suitably selected inorganic base such as K₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as, DMSO, DMF, NMP, and the like; to yield the corresponding compound of formula (XV). Alternatively, the compound of formula (XIII) when Q¹ is hydrogen is reacted with a suitably selected acid, such as, conc. aq. H₂SO₄, and the like; in a suitably selected solvent such as DCM, and the like; to yield the corresponding compound of formula (XV).

Where the compound of formula (XIII) having Q¹ is PG¹, the compound of formula (XIII) is reacted with is reacted with hydrogen peroxide in the presence of a suitably selected inorganic base, such as, K₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as, DMSO, DMF, NMP, and the like; to yield the corresponding compound of formula (XIV), where Q¹ is PG¹. Alternatively, when the compound of formula (XIII) where Q′ is PG¹ is reacted with a suitably selected acid, such as, conc. aq. H₂SO₄, and the like; in a suitably selected solvent, such as DCM, and the like; to yield the corresponding compound of formula (XIV) where Q′ is PG¹. The compound of formula (XIV) is then de-protected according to known methods to remove the PG¹ group and yield the corresponding compound of formula (XV). For example, wherein PG¹ is benzyl, the compound of formula (XIV) is de-protected by reacting with hydrogen in the presence of a suitable selected catalyst such as Pd/C, and the like.

The compound of formula (XV) is reacted with a suitably substituted compound of formula (XVI), wherein LG¹ is a suitably selected leaving group such as Cl, Br, OH, and the like, and wherein LG² is a suitably selected leaving group such as Cl, Br, OH, triflate, B(OH)₂, B(OC₁₋₂alkyl)₂,

and the like, a known compound or compound prepared by known methods; to yield the corresponding compound of formula (XVII).

More particularly, wherein LG¹ is Cl, Br, and the like, the compound of formula (XV) is reacted with the compound of formula (XVI), in the presence of a suitably selected organic base such as pyridine, TEA, DIPEA, and the like; optionally in the presence of DMAP, and the like; in a suitably selected solvent such as DCM, DCE, THF, and the like; to yield the corresponding compound of formula (XVII). Alternatively, wherein LG¹ is OH, and the like, the compound of formula (XV) is reacted with the compound of formula (XVI), in the presence of a suitably selected coupling reagent such as HATU, HBTU, CDI, EDAC, and the like, in the presence of a suitably selected organic base such as pyridine, TEA, DIPEA, and the like; in a suitably selected organic solvent such as NMP, DMF, DCM, DCE, and the like, to yield the corresponding compound of formula (XVII).

The compound of formula (XVII) is reacted (to effect ring closure) with a suitably selected base such as t-BuOK, NaOH, NaOCH₃, LHMDS, and the like; in a suitably selected organic solvent or mixture of solvents such as methanol, ethanol, water, 1,4-dioxane, and the like, and wherein the base in LHMDS, in a suitably selected organic solvent such as THF, and the like; to yield the corresponding compound of formula (XVIII).

The compound of formula (XVIII) is reacted with a suitably substituted compound of formula (XIX), wherein PG² is a suitably selected nitrogen protecting group such as Boc, benzyl, Cbz, benzoyl, and the like, and wherein LG³ is a suitably selected leaving group such as Br, I, Cl, mesylate, tosylate, triflate, and the like, a known compound or compound prepared by known methods; in the presence of a suitably selected base such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent such as DMF, DMP, THF, 1,4-doxane, and the like; to yield the corresponding compound of formula (XX).

The compound of formula (XX) is then de-protected according to known methods to yield the corresponding compound of formula (XXI). For example, wherein PG² is Boc, the compound of formula (XXI) is de-protected by reacting with a suitably selected acid, in a suitably selected organic solvent, for example reacting with HCl in 1,4-dioxane, or reacting with TFA in DCM.

The compound of formula (XXI) is reacted with a suitably substituted compound of formula (XXII), a known compound or compound prepared by known methods, to yield the corresponding compound of formula (XXIII). More particularly, the compound of formula (XXI) is reacted with

(a) a compound of formula (XXII), wherein L^(M) is selected from the group consisting of O═C═N(R^(L))— and S═C═N(R^(L))—; in a suitably selected organic solvent such as DCM, DCE, THF, and the like, to yield the corresponding compound of formula (XXIII) wherein L¹ is —C(O)—N(R^(L))— or —C(S)—N(R^(L))—, respectively;

or (b) a compound of formula (XXII), wherein L^(M) is selected from the group consisting of Cl—C(O)—N(R^(L))— and Cl—C(S)—N(R^(L))—; in the presence of a suitably selected organic base such as pyridine, TEA, DIPEA, and the like; optionally in the presence of DMAP, and the like; in a suitably selected solvent such as DCM, DCE, THF, and the like;

or (c) a compound of formula (XXII), wherein L^(M) is selected from the group consisting of LG⁴-C(O)—, LG⁴-C(S)—, LG⁴-SO₂— and LG⁴-SO₂—N(R^(L))—, wherein LG⁴ is a suitably selected leaving group such as Cl, Br, and the like; in the presence of a suitably selected organic base such as pyridine, TEA, DIPEA, and the like; optionally in the presence of DMAP, and the like; in a suitably selected solvent such as DCM, DCE, THF, and the like;

or (d) a compound of formula (XXII), wherein L^(M) is selected from the group consisting of LG⁴-C(O)—, LG⁴-C(S)—, LG⁴-SO₂— and LG⁴-SO₂—N(R^(L))—, wherein LG⁴ is a suitably selected leaving group such as OH, and the like, in the presence of a suitably selected coupling reagent such as HATU, HBTU, CDI, EDAC, and the like, in the presence of a suitably selected organic base such as pyridine, TEA, DIPEA, and the like; in a suitably selected organic solvent such as NMP, DMF, DCM, DCE, and the like; to yield the corresponding compound of formula (XXIII).

The compound of formula (XXIII) is reacted with a suitably substituted compound of formula (XXIV), wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzuki coupling conditions, more particularly, in the presence of a suitably selected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of a suitably selected inorganic base such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent such as DME, 1,4-dioxane, and the like, preferably mixed with water; to yield the corresponding compound of formula (I).

Alternatively, wherein on the compound of formula (XXIII), LG² is OH, the compound of formula (XXIII) may be reacted with triflic anhydride, in the presence of a suitably selected base such as TEA, pyridine, and the like, in a suitably selected solvent such as DCM, DCE, and the like; to convert the LG² leaving group from OH to triflate; and then reacting the resulting compound with a suitably substituted compound of formula (XXIV), as described above; to yield the corresponding compound of formula (I).

One skilled in the art will recognize that the R⁵ substituent group may alternatively be incorporated into the desired compound of formula (I) by reacting a compound of formula (XXIII), wherein the LG² group is replaced with a group of the formula —B(OR)₂ (wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e., to form the

with a suitably substituted compound of formula (XXIV), wherein the —B(OR)₂ substitutent is replaced with a suitably selected leaving group, such as Cl, Br, triflate, and the like, under Suzuki coupling conditions, more particularly, in the presence of a suitably selected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as DME, 1,4-dioxane, and the like, preferably mixed with water.

Compounds of formula (I) may alternatively be prepared according to the process as outlined in Scheme 2, below.

Accordingly, a suitably substituted compound of formula (XVIII), prepared for example as outlined in Scheme 1 above, is reacted with a suitably substituted compound of formula (XXIV), wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzuki coupling conditions, more particularly, in the presence of a suitably selected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as DME, 1,4-dioxane, and the like, preferably mixed with water; to yield the corresponding compound of formula (XV).

The compound of formula (XV) is reacted with a suitably substituted compound of formula (XIX), wherein PG² is a suitably selected nitrogen protecting group, such as Boc, benzyl, Cbz, benzoyl, and the like, and wherein LG³ is a suitably selected leaving group such as Br, I, Cl, mesylate, tosylate, triflate, and the like, a known compound or compound prepared by known methods; in the presence of a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, and the like; to yield the corresponding compound of formula (XXVI).

The compound of formula (XXVI) is de-protected according to known methods to yield the corresponding compound of formula (XVII). For example, wherein PG² is Boc, the compound of formula (XVI) is de-protected by reacting with a suitably selected acid, in a suitably selected organic solvent, for example reacting with HCl in 1,4-dioxane, or reacting with TFA in DCM.

The compound of formula (XVII) is then further reacted with a suitably substituted compound of formula (XXII), a known compound or compound prepared by known methods, as outlined in more detail in Scheme 1 above; to yield the corresponding compound of formula (I).

Compounds of formula (I) may alternatively be prepared according to the process as outlined in Scheme 3, below.

Accordingly, a suitably substituted compound of formula (XVIII), prepared for example as outlined in Scheme 1 above, is reacted with a suitably substituted compound of formula (XXVIII), wherein LG⁵ is a suitably selected leaving group, such as Cl, Br, I, mesylate, tosylate triflate, and the like, a known compound or compound prepared as described herein; in the presence of a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, and the like; to yield the corresponding compound of formula (XXIX).

The compound of formula (XXIX) is reacted with a suitably substituted compound of formula (XXIV), wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e. to form the

a known compound or compound prepared by known methods, under Suzuki coupling conditions, more particularly, in the presence of a suitably selected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as DME, 1,4-dioxane, and the like, preferably mixed with water; to yield the corresponding compound of formula (I).

Alternatively, a suitably substituted compound of formula (XXV), prepared for example, as described in Scheme 2 above, is reacted with a suitably substituted compound of formula (XVIII), prepared for example as outlined in Scheme 1 above, is reacted with a suitably substituted compound of formula (XXVIII), wherein LG⁵ is a suitably selected leaving group, such as Cl, Br, I, mesylate, tosylate, triflate, and the like, a known compound or compound prepared as described herein; in the presence of a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, and the like; to yield the corresponding compound of formula (I).

The compound of formula (XXVIII) is a known compound or a compound that may be prepared, for example, according to the process outlined in Scheme 4, below.

Accordingly, a suitably substituted compound of formula (XXX), a known compound or compound prepared by known methods (for example, by de-protecting the corresponding known, nitrogen-protected compound), is reacted with a suitably substituted compound of formula (XXII), a known compound or compound prepared by known methods, to yield the corresponding compound of formula (XXIII), according to the process as outlined in Scheme 1 above; to yield the corresponding compound of formula (XXXI).

The compound of formula (XXXI) is reacted with a suitably selected source of chlorine, such as POCl₃, SOCl₂, and the like; or suitably selected source of bromine, such as PBr₃, POBr₃, CBr₄ in combination with PPh₃, and the like; or suitably selected source of iodine, such as I₂ in the presence of PPh₃; or suitably selected source of mesylate, such as MsCl, and the like; or other suitable selected source of any other suitable LG⁵ leaving group; according to known methods; to yield the corresponding compound of formula (XXVIII).

Compounds of formula (XXV) may be prepared, for example, according to the process outlined in Scheme 5, below.

Accordingly, a suitably substituted compound of formula (XV), prepared for example as described in Scheme 1 above, is reacted with a suitably substituted compound of formula (XXXII), wherein LG⁶ wherein LG¹ is a suitably selected leaving group, such as Cl, Br, OH, and the like, to yield the corresponding compound of formula (XXXIII).

More particularly, wherein LG⁶ is is Cl, Br, and the like, the compound of formula (XV) is reacted with the compound of formula (XXXII), in the presence of a suitably selected organic base, such as pyridine, TEA, DIPEA, and the like; optionally in the presence of DMAP, and the like; in a suitably selected solvent such as DCM, DCE, THF, and the like. Alternatively, wherein LG⁶ is OH, and the like, the compound of formula (XV) is reacted with the compound of formula (XXXII), in the presence of a suitably selected coupling reagent, such as HATU, HBTU, CDI, EDAC, and the like, in the presence of a suitably selected organic base, such as pyridine, TEA, DIPEA, and the like; in a suitably selected organic solvent, such as NMP, DMF, DCM, DCE, and the like.

The compound of formula (XXXIII) is reacted (to effect ring closure) with a suitably selected base, such as t-BuOK, NaOH, NaOCH₃, LHMDS, and the like; in a suitably selected organic solvent or mixture of solvents, such as methanol, ethanol, water, 1,4-dioxane, and the like, and wherein the base in LHMDS, in a suitably selected organic solvent, such as THF, and the like; to yield the corresponding compound of formula (XXV).

The compound of formula (XXV) is reacted with a suitably substituted compound of formula (XXVIII), wherein LG⁵ is a suitably selected leaving group, such as Cl, Br, I, mesylate, tosylate, triflate, and the like, a known compound or compound prepared as described herein; in the presence of a suitably selected base, such as K₂CO₃, Na₂CO₃, NaH, and the like; in a suitably selected solvent, such as DMF, DMP, THF, 1,4-doxane, and the like; to yield the corresponding compound of formula (I).

One skilled in the art will recognize that the compound of formula (XXV) may alternatively be reacted with a suitably substituted compound of formula (XIX), the product de-protected and then further reacted with a suitably substituted compound of formula (XXII), to yield the corresponding compound of formula (I); as described in for, Scheme 1 or Scheme 2, above; to yield the corresponding compound of formula (I).

The compound of formula (XXIV) is a known compound or compound prepared for example, as described in Scheme 6, below.

Accordingly, a suitable substituted compound of formula (XXXIV), wherein Q² is hydrogen or a suitably selected oxygen protecting group, such as benzyl, C₁₋₄alkyl (preferably methyl, ethyl, or t-butyl), and the like, and wherein LG¹ is a suitably selected leaving group, such as Cl, Br, I, triflate, and the like, a known compound or compound prepared by known methods, is reacted with a suitably substituted compound of formula (XXIV), wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e., to form the

a known compound or compound prepared by known methods, under Suzuki coupling conditions, more particularly, in the presence of a suitably selected catalysts or catalyst system, such as Pd(PPh₃)₄, Pd₂(dba)₃, Pd(dppf), a mixture of Pd(OAc)₂ and PPh₃, and the like; in the presence of a suitably selected inorganic base, such as K₂CO₃, Cs₂CO₃, Na₂CO₃, and the like; in a suitably selected solvent, such as DME, 1,4-dioxane, and the like, preferably mixed with water; to yield the corresponding compound of formula (XXXV).

The compound of formula (XXXV) is reacted to yield the corresponding compound of formula (XXXII). More particularly, wherein Q² is hydrogen, the compound of formula (XXXV) is reacted with a suitably selected source of chlorine, such as POCl₃, SOCl₂, and the like; or suitably selected source of bromine, such as PBr₃, and the like; or suitably selected source of iodine, such as I₂ in the presence of PPh₃; according to known methods; to yield the corresponding compound of formula (XXXII) wherein LG⁶ is chloro, bromo or iodo, respectively. Alternatively, wherein Q² is a suitably selected oxygen protecting group, for example, benzyl, the compound of formula (XXXV) is de-protected by hydrogenolysis (reacting with hydrogen in the presence of a Pd/C catalyst), according to known methods; according to known methods, to yield the corresponding compound of formula (XXXII) wherein LG⁶ is OH. Alternatively still, wherein Q² is a suitably selected oxygen protecting group such as t-butyl, the compound of formula (XXXV) is de-protected by with a suitably selected acid, in a suitably selected organic solvent, according to known methods (e.g., with HCl in 1,4-dioxane or with TFA in DCM), to yield the corresponding compound of formula (XXXII) wherein LG⁶ is OH. Alternatively still, wherein Q² is a suitably selected oxygen protecting group, such as C₁₋₄alkyl, and the like, for example methyl or ethyl, the compound of formula (XXXV) is de-protected by reacting with a suitably selected base, in a suitably selected mixture of water and an organic solvent, according to known methods (for example reacting with NaOH or KOH in a mixture of water, THF and methanol), to yield the corresponding compound of formula (XXXII), wherein LG⁶ is OH.

Compounds of formula (I) may alternatively be prepared according to the process outlined in Scheme 7, below.

Accordingly, a suitably substituted compound of formula (XXXVI), wherein Q³ is hydrogen or a suitably selected oxygen protecting group, such as benzyl, C₁₋₄alkyl (preferably methyl, ethyl or t-butyl), and the like, a known compound or compound prepared by known methods, is reacted with a suitably substituted compound of formula (XVI), wherein LG¹ is a suitably selected leaving group, such as Cl, Br, OH, and the like, and wherein LG² is a suitably selected leaving group, such as Cl, Br, OH, triflate, B(OH)₂, B(OC₁₋₂alkyl)₂,

and the like, a known compound or compound prepared by known methods; according to known methods, for example, according to the process as outlined in Scheme 1 above; to yield the corresponding compound of formula (XXXVII), wherein Q⁴ is the corresponding LG² group.

Alternatively, a suitably substituted compound of formula (XXXVI), wherein Q³ is hydrogen or a suitably selected oxygen protecting group such as benzyl, C₁₋₄alkyl (preferably methyl, ethyl or t-butyl), and the like, a known compound or compound prepared by known methods; is reacted with a suitably substituted compound of formula (XXXII), wherein LG⁶ is a suitably selected leaving group, such as Cl, Br, OH, and the like, a known compound or compound prepared by known methods; according to known methods, for example, according to the process as outlined in Scheme 5 above; to yield the corresponding compound of formula (XXXVII) wherein Q⁴ is R⁵.

The compound of formula (XXXVII) is then reacted to yield the corresponding compound of formula (XXXVIII). More particularly, wherein

(a) Q³ is hydrogen, the compound of formula (XXXVII) is reacted with ammonia or a suitably selected source of ammonia such as NH₄Cl, NH₄OH, gaseous NH₃, and the like; in the presence of a suitably selected coupling reagent, such as HATU, HBTU, CDI, EDAC, and the like, in the presence of a suitably selected organic base, such as pyridine, TEA, DIPEA, and the like; in a suitably selected organic solvent, such as NMP, DMF, DCM, DCE, and the like; to yield the corresponding compound of formula (XXXVIII);

(b) Q³ is a suitably selected oxygen protecting group, such as methyl, ethyl and the like, the compound of formula (XXXVII) is reacted with ammonia or a suitably selected source of ammonia, such as concentrated NH₄OH, NH₄Cl, gaseous NH₃, and the like, according to known methods (for example as described in (a) above), to yield the corresponding compound of formula (XXXVIII);

or (c) wherein Q³ is a suitably selected oxygen protecting group, such as benzyl, t-butyl, and the like, the compound of formula (XXXVII) is de-protected according to known methods (e.g., wherein Q² is benzyl, t-butyl and the like, by hydrogenolysis, reacting with hydrogen in the presence of a catalyst such as Pd/C), or by reacting with a suitably selected acid, in a suitably selected organic solvent (e.g., reacting with HCl, in 1,4-dioxane or reacting with TFA in DCM) to yield the corresponding compound of formula (XXXVII) wherein Q³ is hydrogen; such compound is then reacted with ammonia or a suitably selected source of ammonia as described in (a) above, to yield the corresponding compound of formula (XXXVIII).

The compound of formula (XXXVIII) is reacted (to effect ring closure) with a suitably selected base, such as t-BuOK, NaOH, NaOCH₃, LHMDS, and the like; in a suitably selected organic solvent or mixture of solvents, such as methanol, ethanol, water, 1,4-dioxane, and the like, and wherein the base in LHMDS, in a suitably selected organic solvent, such as THF, and the like; to yield the corresponding compound of formula (XXXIX).

The compound of formula (XXXIX) is reacted, according to the procedures as described herein, to yield the desired compound of formula (I). For example, the compound of formula (XXXIX), wherein Q⁴ is a suitably elected leaving group, may be substituted for the compound of formula (XVIII) in Scheme 1 reacted according to the procedure as described in Scheme 1, to yield the desired compound of formula (I). Alternatively, the compound of formula (XXXIX), wherein Q⁴ is R⁵, may be substituted for the compound of formula (XV) in Scheme 2 or the compound of formula (XXV) in Scheme 3, and reacted as described therein, respectively, to yield the corresponding compound of formula (I).

Compounds of formula (I), wherein R¹ and R² are taken together with the carbon atom to which they are bound to form an optionally substituted 4 to 8-membered, saturated heterocyclyl of the formula

wherein p and q are each independently selected to be an integer from 0 to 2, and wherein the “•” denotes the carbon atom of the spiro attachment to the imidazolidin-5-one core, may alternatively prepared as described in Scheme 8, below.

Accordingly, a suitably substituted compound of formula (XL) wherein PG⁴ is a suitably selected nitrogen protecting group, such as Boc, Cbz, benzyl, and the like, wherein Q⁴ is —R⁵ or a suitably selected leaving group, such as Cl, Br, I, OH, and the like, and wherein Q⁵ is -L¹-R³ or a suitably selected nitrogen protecting group such as Boc, benzyl, Cbz, and the like; and wherein Q⁵ is a nitrogen protecting group, then preferably, PG⁴ and the Q⁵ nitrogen protecting group are selected such that the two nitrogen protecting groups are removed under different conditions (i.e., the two nitrogen protecting groups are different and are selected such that each may be selectively removed without removing the other), a known compound or compound prepared by known methods, for example, as described in Scheme 1 above, is de-protected to remove the PG⁴ group, according to known methods, to yield the corresponding compound of formula (XLI). For example, wherein PG⁴ is Boc, the compound of formula (XL) may be de-protected by reacting with a suitably selected acid, such as HCl, and the like, in a suitably selected organic solvent, such as 1,4-dioxane, and the like.

The compound of formula (XLI) is then reacted to yield the corresponding compound of formula (I). Wherein the compound of formula (XLI) Q⁴ is —R⁵ and Q⁵ is -L¹-R³, then the compound of formula (XLI) is reacted with a suitably selected compound of formula (XLII), wherein LG⁸ is OH or a suitably selected leaving group, such as Cl, Br, mesylate, tosylate, and the like, a known compound or compound prepared by known methods, according to known methods readily recognized by those skilled in the art, e.g., alkylation, peptide coupling, and the like, to yield the corresponding compound of formula (I). Alternatively, the compound of formula (XLI) may be reacted with a suitably selected compound of formula (XLII) wherein LG⁸ includes an aldehyde or ketone carbonyl group, as would be readily recognized by one skilled in the art, under reductive amination conditions as known in the art, (for example, reacting with sodium triacetoxyborohydride and acetic acid, in a suitably selected solvent, such as DCM, DCE, THF, and the like; or reacting with cyanoborohydride in a suitably selected solvent, such as methanol, and the like), to yield the corresponding compound of formula (I).

Wherein the compound of formula (XLI) Q⁴ is a suitably selected leaving group and/or Q⁵ is a suitably selected nitrogen protecting group, then the compound of formula (XLI) may alternatively be reacted to: (a) attach the R⁵ group by reacting with, for example, a suitably substituted compound of formula (XXIV), as described in, for example, Scheme 1, above; (b) remove of the Q⁵ nitrogen protecting group and then attach the -L¹-R³ group by reacting with, for example, a suitably substituted compound of formula (XXII), as described in, for example, Scheme 1 above; and (c) attach the —R¹° group, as described above; in any order or sequence; to yield the corresponding compound of formula (I).

One skilled in the art will recognize that the compounds of formula (I) of the present invention may be prepared according to the methods as described herein, or alternatively by attaching substituent groups, such as

etc., and effecting ring closure to form the imidazolidin-4-one ring core, in any order or sequence, protecting and de-protecting reactive groups, as necessary or desirable, according to methods as described herein or known to those skilled in the art. One skilled in the art will further recognize that some such sequences may result in reaction steps with better reactivity profiles, yields and/or selectivity, and thus may be more efficient or desirable than other routes.

One skilled in the art will further recognize that when any of the coupling steps described above a reactant is substituted with a suitably selected leaving group, such as OH, triflate, and the like, such coupling may alternatively be effected by converting the leaving group to a group of the formula —B(OR)₂, wherein the two R groups are each H, are each the same C₁₋₂alkyl or are taken together as —C(CH₃)₂—C(CH₃)₂— to form a ring (i.e., to form the

and then completing the coupling under Suzuki coupling conditions, as herein described and known to those skilled in the art.

The present invention further comprises pharmaceutical compositions containing one or more compounds of formula (I) with a pharmaceutically acceptable carrier. Pharmaceutical compositions containing one or more of the compounds of the invention described herein as an active ingredient can be prepared by intimately mixing the compound or compounds with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier may take a wide variety of forms depending upon the desired route of administration (e.g., oral, parenteral). Thus, for liquid oral preparations, such as suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, stabilizers, coloring agents and the like; for solid oral preparations, such as powders, capsules, and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Solid oral preparations may also be coated with substances such as sugars or be enteric-coated so as to modulate major site of absorption. For parenteral administration, the carrier will usually include sterile water and other ingredients may be added to increase solubility or preservation. Injectable suspensions or solutions may also be prepared utilizing aqueous carriers along with appropriate additives.

To prepare the pharmaceutical compositions of this invention, one or more compounds of the present invention as an active ingredient is intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, such carrier may take a wide variety of forms depending of the form of preparation desired for administration, e.g., oral or parenteral such as intramuscular. In preparing the compositions in oral dosage form, any of the usual pharmaceutical media may be employed. Thus, for liquid oral preparations, such as, for example, suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents and the like; for solid oral preparations such as, for example, powders, capsules, caplets, gelcaps and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Because of their ease in administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques. For parenterals, the carrier will usually include sterile water, through other ingredients, for example, for purposes such as aiding solubility or for preservation, may be included. Injectable suspensions may also be prepared, in which case appropriate liquid carriers, suspending agents and the like may be employed. The pharmaceutical compositions herein will contain, per dosage unit, e.g., tablet, capsule, powder, injection, teaspoonful and the like, an amount of the active ingredient necessary to deliver an effective dose as described above. The pharmaceutical compositions herein will contain, per unit dosage unit, e.g., tablet, capsule, powder, injection, suppository, teaspoonful and the like, of from about 0.01 mg to about 1000 mg or any amount or range therein, and may be given at a dosage of from about 0.01 mg/kg/day to about 300 mg/kg/day, or any amount or range therein, preferably from about 0.1 mg/kg/day to about 100 mg/kg/day, or any amount or range therein, preferably from about 0.50 mg/kg/day to about 50 mg/kg/day, or any amount or range therein, preferably from about 0.75 mg/kg/day to about 15 mg/kg/day, or any amount or range therein, preferably from about 1.0 mg/kg/day to about 7.5 mg/kg/day, or any amount or range therein, preferably from about 1.5 mg/kg/day to about 5.0 mg/kg/day, or any amount or range therein. The dosages, however, may be varied depending upon the requirement of the patients, the severity of the condition being treated and the compound being employed. The use of either daily administration or post-periodic dosing may be employed.

Preferably these compositions are in unit dosage forms, such as tablets, pills, capsules, powders, granules, sterile parenteral solutions or suspensions, metered aerosol or liquid sprays, drops, ampoules, autoinjector devices or suppositories; for oral parenteral, intranasal, sublingual or rectal administration, or for administration by inhalation or insufflation. Alternatively, the composition may be presented in a form suitable for once-weekly or once-monthly administration; for example, an insoluble salt of the active compound, such as the decanoate salt, may be adapted to provide a depot preparation for intramuscular injection. For preparing solid compositions, such as tablets, the principal active ingredient(s) is mixed with a pharmaceutical carrier, e.g., conventional tableting ingredients, such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gums, and other pharmaceutical diluents, e.g., water, to form a solid preformulation composition containing a homogeneous mixture of a compound of the present invention, or a pharmaceutically acceptable salt thereof. When referring to these preformulation compositions as homogeneous, it is meant that the active ingredient is dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective dosage forms such as tablets, pills and capsules. This solid preformulation composition is then subdivided into unit dosage forms of the type described above containing from about 0.01 mg to about 1,000 mg, or any amount or range therein, of the active ingredient of the present invention. The tablets or pills of the novel composition can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permits the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials include a number of polymeric acids with materials, such as as shellac, cetyl alcohol and cellulose acetate.

The liquid forms in which the compositions of the present invention may be incorporated for administration orally or by injection include, aqueous solutions, suitably flavoured syrups, aqueous or oil suspensions, and flavoured emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil, as well as elixirs and similar pharmaceutical vehicles. Suitable dispersing or suspending agents for aqueous suspensions, include synthetic and natural gums, such as tragacanth, acacia, alginate, dextran, sodium carboxymethylcellulose, methylcellulose, polyvinyl-pyrrolidone or gelatin.

The method of treating disorders described in the present invention may also be carried out using a pharmaceutical composition including any of the compounds as defined herein and a pharmaceutically acceptable carrier. The pharmaceutical composition may contain between about 0.01 mg and about 1000 mg of the compound, or any amount or range therein; preferably from about 1.0 mg to about 500 mg of the compound, or any amount or range therein, and may be constituted into any form suitable for the mode of administration selected. Carriers include necessary and inert pharmaceutical excipients, including, but not limited to, binders, suspending agents, lubricants, flavorants, sweeteners, preservatives, dyes, and coatings. Compositions suitable for oral administration include solid forms, such as pills, tablets, caplets, capsules (each including immediate release, timed release and sustained release formulations), granules, and powders, and liquid forms, such as solutions, syrups, elixers, emulsions, and suspensions. Forms useful for parenteral administration include sterile solutions, emulsions and suspensions.

Advantageously, compounds of the present invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily. Furthermore, compounds for the present invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal skin patches well known to those of ordinary skill in that art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen.

For instance, for oral administration in the form of a tablet or capsule, the active drug component can be combined with an oral, pharmaceutically acceptable inert carrier, such as ethanol, glycerol, water and the like. Moreover, when desired or necessary, suitable binders; lubricants, disintegrating agents and coloring agents can also be incorporated into the mixture. Suitable binders include, without limitation, starch, gelatin, natural sugars, such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrators include, without limitation, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.

The liquid forms in suitably flavored suspending or dispersing agents such as the synthetic and natural gums, e.g., tragacanth, acacia, methyl-cellulose and the like. For parenteral administration, sterile suspensions and solutions are desired. Isotonic preparations that generally contain suitable preservatives are employed when intravenous administration is desired.

To prepare a pharmaceutical composition of the present invention, a compound of formula (I) as the active ingredient is intimately admixed with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques, which carrier may take a wide variety of forms depending of the form of preparation desired for administration (e.g., oral or parenteral). Suitable pharmaceutically acceptable carriers are well known in the art. Descriptions of some of these pharmaceutically acceptable carriers may be found in The Handbook of Pharmaceutical Excipients, published by the American Pharmaceutical Association and the Pharmaceutical Society of Great Britain.

Methods of formulating pharmaceutical compositions have been described in numerous publications such as Pharmaceutical Dosage Forms: Tablets, Second Edition, Revised and Expanded, Volumes 1-3, edited by Lieberman et al; Pharmaceutical Dosage Forms: Parenteral Medications, Volumes 1-2, edited by Avis et al; and Pharmaceutical Dosage Forms: Disperse Systems, Volumes 1-2, edited by Lieberman et al; published by Marcel Dekker, Inc.

Compounds of this invention may be administered in any of the foregoing compositions and according to dosage regimens established in the art whenever treatment of disorders mediated by inhibition of fatty acid synthase (FASN) enzyme, as described herein, is required.

The daily dosage of the products may be varied over a wide range from about 0.01 mg to about 1,000 mg per adult human per day, or any amount or range therein. For oral administration, the compositions are preferably provided in the form of tablets containing about 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 150, 200, 250, 500 and 1000 milligrams of the active ingredient each for the symptomatic adjustment of the dosage to the patient to be treated. An effective amount of the drug is ordinarily supplied at a dosage level of from about 0.01 mg/kg to about 300 mg/kg of body weight per day, or any amount or range therein. Preferably, the range is from about 0.5 to about 50.0 mg/kg of body weight per day, or any amount or range therein. More preferably, from about 0.75 to about 15.0 mg/kg of body weight per day, or any amount or range therein. More preferably, from about 1.0 to about 7.5 mg/kg of body weight per day, or any amount or range therein. The compounds may be administered on a regimen of 1 to 4 times per day.

Optimal dosages to be administered may be readily determined by those skilled in the art, and will vary with the particular compound used, the mode of administration, the strength of the preparation, the mode of administration, and the advancement of the disease condition. In addition, factors associated with the particular patient being treated, including patient age, weight, diet and time of administration, will result in the need to adjust dosages.

One skilled in the art will recognize that, both in vivo and in vitro trials using suitable, known and generally accepted cell and/or animal models are predictive of the ability of a test compound to treat or prevent a given disorder.

One skilled in the art will further recognize that human clinical trails including first-in-human, dose ranging and efficacy trials, in healthy patients and/or those suffering from a given disorder, may be completed according to methods well known in the clinical and medical arts.

The following Examples are set forth to aid in the understanding of the invention, and are not intended and should not be construed to limit in any way the invention set forth in the claims that follow thereafter.

SYNTHESIS EXAMPLES

In the following Examples, some synthesis products are listed as having been isolated as a residue. It will be understood by one of ordinary skill in the art that the term “residue” does not limit the physical state in which the product was isolated and may include, for example, a solid, an oil, a foam, a gum, a syrup, and the like.

Example 1 2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4,4]non-1-en-4-one (Compound #2)

STEP A: 4-Bromo-N-(1-carbamoylcyclopentyl)benzamide

A mixture 1-aminocyclopentanecarboxamide (0.5 g, 3.9 mmol), 4-bromobenzoic acid (0.784 g, 3.9 mmol), EDCI (0.747 g, 3.9 mmol), HOBt (0.527 g, 3.9 mmol) and DIEA (0.67 mL, 3.9 mmol) in DMF (10 mL) was stirred at room temperature for 1 day. The reaction mixture was partitioned between EtOAc and aqueous saturated NaHCO₃. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 4-bromo-N-(1-carbamoylcyclopentyl)benzamide (1.2 g, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.54-1.82 (m, 3H), 1.89-2.04 (m, 2H), 2.04-2.23 (m, 2H), 6.76 (br. s., 1H), 7.09 (br. s., 1H), 7.66 (d, J=8.6 Hz, 2H), 7.83 (d, J=8.6 Hz, 2H), 8.36 (s, 1H); MS m/z 313.0 (M+H)⁺.

STEP B: 2-(4-Bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one

A mixture of 4-bromo-N-(1-carbamoylcyclopentyl)benzamide (1.0 g, 3.21 mmol) and NaOH (0.64 g, 16.06 mmol) in H₂O (3.25 mL) and MeOH (50 mL) was stirred at 65° C. for 1 day. The reaction mixture was partitioned between water (300 mL) and EtOAc (300 mL). The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (0.9 g, 95%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.69-1.79 (m, 2H), 1.80-1.92 (m, 6H), 5.76 (s, 1H), 7.74 (d, J=8.3 Hz, 2H), 7.90 (d, J=7.6 Hz, 2H); MS m/z 295.0 (M+H)⁺.

STEP C: (S)-tert-Butyl 3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate

To a stirring solution of 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (50 mg, 0.17 mmol) and (R)-tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate (90.1 mg, 0.34 mmol) in DMF (3 mL) was added Cs₂CO₃ (139 mg, 0.42 mmol). After stirring at room temperature for 1 h and 65° C. for 17 h, the reaction mixture was partitioned between aqueous NaHCO₃ and EtOAc. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 40% EtOAc/heptane) to yield (S)-tert-butyl 3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (62 mg, 76%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.42 (s, 9H), 1.74-1.82 (m, 1H), 1.82-1.91 (m, 2H), 1.91-2.10 (m, 7H), 2.24 (dt, J=14.7, 7.4 Hz, 1H), 2.73-2.89 (m, 1H), 3.11-3.40 (m, 3H), 3.49-3.68 (m, 2H), 7.45 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.1 Hz, 2H); MS m/z 476.1 (M+H)⁺.

STEP D: (R)-2-(4-Bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of (S)-tert-butyl 3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (270 mg, 0.56 mmol) in 1,4-dioxane was added 4M HCl in 1,4-dioxane (17 mL). After stirring overnight at room temperature the reaction mixture was concentrated to yield (R)-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one, as its corresponding HCl salt, as a solid, which was directly used into the next step; MS m/z 376 (M+H)⁺.

STEP E: (R)-2-(4-Bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of (R)-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one HCl salt (234 mg, 0.56 mmol) in DCM (15 mL) and DIPEA (0.21 mL, 1.25 mmol) was added cyclopropanecarbonyl chloride (0.053 mL, 0.56 mmol). After stirring at room temperature for 3 h, the reaction mixture was partitioned between aqueous NaHCO₃ and DCM. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield (R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (250 mg, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.58-0.74 (m, 4H), 1.40-1.64 (m, 1H), 1.68 (td, J=12.0, 6.8 Hz, 1H), 1.73-1.83 (m, 3H), 1.88 (br. s., 6H), 2.04-2.14 (m, 1H), 2.80 (dd, J=11.6, 7.1 Hz, 1H), 3.03-3.14 (m, 1H), 3.17-3.28 (m, 1H), 3.38-3.55 (m, 2H), 3.58 (t, J=8.1 Hz, 2H), 7.60-7.68 (m, 2H), 7.71-7.78 (m, 2H); MS m/z 444.1 (M+H)⁺.

STEP F: (R)-2-(4-(Benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one, Compound #2

To a solution of (R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (150 mg, 0.338 mmol) and benzofuran-5-ylboronic acid (86.32 mg, 0.506 mol) in DME (3 mL) was added under argon aqueous 2M Na₂CO₃ (0.35 mL, 0.709 mmol) and Pd(PPh₃)₄ (15 mg, 0.013 mmol). The reaction mixture was refluxed for 16 h, filtered and concentrated in vacuo and the resulting residue was purified by preparative reverse-phase chromatography to yield (R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (80 mg, 49%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.66-0.77 (m, 2H), 0.86-1.01 (m, 2H), 1.23-1.75 (m, 3H), 1.78-2.17 (m, 9H), 2.28-2.56 (m, 1H), 2.99-3.25 (m, 1H), 3.26-3.57 (m, 2H), 3.57-3.82 (m, 3H), 6.85 (s, 1H), 7.56 (d, 1H), 7.61 (d, 1H), 7.64-7.71 (m, 3H), 7.73-7.80 (m, 2H), 7.84 (s, 1H); MS m/z 482.3 (M+H)⁺.

Following the procedure described in Example 1, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following intermediate compounds were prepared:

Following the procedure described in Example 1, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  75

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)piperidin-4- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70 (dd, J = 7.8, 3.2 Hz, 2 H), 0.87-0.95 (m, 2 H), 0.95-1.02 (m, 1 H), 1.02-1.17 (m, 1 H), 1.40-1.62 (m, 2 H), 1.63-1.72 (m, 1 H), 1.73-1.84 (m, 2 H), 1.85-2.15 (m, 8 H), 2.47 (t, J = 11.7 Hz, 1 H), 2.97 (t, J = 12.5 Hz, 1 H), 3.57 (dd, J = 15.7, 7.1 Hz, 2 H), 4.07-4.22 (m, 1 H), 4.51 (d, J = 12.2 Hz, 1 H), 6.85 (d, J = 2.0 Hz, 1 H), 7.52-7.60 (m, 2 H), 7.62-7.66 (m, 2 H), 7.69 (d, J = 2.2 Hz, 1 H), 7.75 (d, J = 8.3 Hz, 2 H), 7.85 (s, 1 H); MS m/z 496.2 (M + H)⁺.  76

3-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.71 (dd, J = 7.8, 3.2 Hz, 2 H), 0.83-0.96 (m, 2 H), 0.96-1.03 (m, 1 H), 1.03-1.19 (m, 1 H), 1.47 (br. s., 1 H), 1.56 (br. s., 1 H), 1.62-1.72 (m, 1 H), 1.72-1.86 (m, 2 H), 1.87-2.16 (m, 9 H), 2.46 (t, J = 12.2 Hz, 1 H), 2.96 (t, J = 12.0 Hz, 1 H), 3.58 (dd, J = 9.8, 8.1 Hz, 2 H), 4.50 (br. s., 1 H), 6.63 (br. s., 1 H), 7.26 (br. s., 1 H), 7.43-7.52 (m, 2 H), 7.62 (d, J = 8.3 Hz, 2 H), 7.78 (d, J = 8.1 Hz, 2 H), 7.92 (s, 1 H), 8.61 (br. s., 1 H); MS m/z 495.3 (M + H)⁺  77

3-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.62- 0.77 (m, 2 H), 0.85-1.03 (m, 3 H), 1.03- 1.16 (m, 1 H), 1.41-1.63 (m, 2 H), 1.63- 1.71 (m, 1 H), 1.81 (m, J = 11.3, 7.5, 3.8, 3.8 Hz, 1 H), 1.88-2.17 (m, 8 H), 2.46 (t, J = 11.5 Hz, 1 H), 2.97 (t, J = 12.5 Hz, 1 H), 3.50-3.70 (m, 2 H), 4.04-4.23 (m, 1 H), 4.50 (d, J = 12.0 Hz, 1 H), 7.63-7.77 (m, 3 H), 7.81-7.95 (m, 3 H), 8.03-8.15 (m, 2 H), 8.59 (d, J = 5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 507.3 (M + H)⁺  78

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (dd, J = 7.6, 3.5 Hz, 2 H), 0.92-1.03 (m, 2 H), 1.24-1.38 (m, 1 H), 1.96-2.25 (m, 6 H), 2.25-2.39 (m, 2 H), 2.80-2.98 (m, 1 H), 3.70 (br. s., 1 H), 3.85-4.41 (m, 5 H), 6.65 (br. s., 1 H), 7.30 (br. s., 1 H), 7.45 (d, 1 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 2 H), 7.88 (d, J = 8.1 Hz, 2 H), 7.93 (s, 1 H), 8.52 (br. s., 2 H); MS m/z 467.0 (M + H)⁺  79

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70 (dd, J = 7.3, 3.8 Hz, 2 H), 0.84-0.96 (m, 2 H), 1.23-1.34 (m, 1 H), 1.71-2.16 (m, 10 H), 2.70-2.84 (m, 1 H), 3.57 (dd, J = 9.9, 5.8 Hz, 1 H), 3.82-4.05 (m, 4 H), 7.72 (d, J = 8.1 Hz, 2 H), 7.75 (d, J = 6.1 Hz, 1 H), 7.88 (d, J = 8.1 Hz, 2 H), 7.91 (d, 1 H), 8.07 (s, 1 H), 8.12 (d, J = 8.6 Hz, 1 H), 8.60 (d, J = 5.6 Hz, 1 H), 9.33 (s, 1 H); MS m/z 478.9 (M + H)⁺  80

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (dd, J = 7.3, 3.3 Hz, 2 H), 0.88-1.03 (m, 2 H), 1.21-1.38 (m, 1 H), 1.99-2.29 (m, 8 H), 2.79-2.98 (m, 1 H), 3.68 (br. s., 1 H), 3.90-4.23 (m, 4 H), 4.24-4.41 (m, 1 H), 6.87 (s, 1 H), 7.57 (d, J = 8.6 Hz, 1 H), 7.63 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.5 Hz, 1 H), 7.75-7.83 (m, 2 H), 7.84-7.92 (m, 3 H); MS m/z 468.0 (M + H)⁺  74

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-isoquinolin-6-yl-2- methylphenyl)-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.56- 0.68 (m, 4 H), 1.27-1.66 (m, 2 H), 1.69- 1.98 (m, 9 H), 2.10-2.34 (m, 1 H), 2.39 (s, 3 H), 2.74-3.32 (m, 3 H), 3.36-3.59 (m, 3 H), 7.62 (dd, J = 18.4, 7.8 Hz, 1 H), 7.81- 7.88 (m, 1 H), 7.91 (d, J = 5.6 Hz, 2 H), 8.10 (d, J = 8.6 Hz, 1 H), 8.25 (d, J = 8.6 Hz, 1 H), 8.38 (s, 1 H), 8.55 (d, J = 5.6 Hz, 1 H), 9.37 (s, 1 H); MS m/z 506.9 (M + H)⁺  1

4′-(3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4-oxo-1,3-diazaspiro[4.4]non-1- en-2-yl)biphenyl-4-carbonitrile ¹H NMR (400 MHz, CDCl₃) δ ppm 0.64- 0.78 (m, 2 H), 0.86-1.01 (m, 2 H), 1.39- 1.88 (m, 3 H), 1.88-2.15 (m, 8 H), 2.25- 2.54 (m, 1 H), 2.92-3.27 (m, 1 H), 3.27- 3.58 (m, 2 H), 3.58-3.83 (m, 3 H), 7.69- 7.82 (m, 8 H); MS m/z 467.3 (M + H)⁺  66

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-quinolin-5-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.68- 0.78 (m, 2 H), 0.88-1.03 (m, 2 H), 1.42- 2.01 (m, 6 H), 2.02-2.16 (m, 4 H), 2.34- 2.61 (m, 1 H), 2.99-3.61 (m, 3 H), 3.62- 3.84 (m, 3 H), 7.36-7.44 (m, 1 H), 7.55 (d, J = 7.1 Hz, 1 H), 7.59-7.67 (m, 2 H), 7.70- 7.77 (m, 2 H), 7.80 (t, J = 7.8 Hz, 1 H), 8.19 (dt, J = 8.5, 4.6 Hz, 2 H), 8.97 (d, J = 4.0 Hz, 1 H); MS m/z 493.2 (M + H)⁺  67

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-isoquinolin-5-ylphenyl)- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.73 (dd, J = 7.8, 3.3 Hz, 2 H), 0.88-1.03 (m, 2 H), 1.44-1.76 (m, 2 H), 1.76-2.18 (m, 9 H), 2.34-2.62 (m, 1 H), 2.99-3.31 (m, 1 H), 3.31-3.62 (m, 2 H), 3.62-3.85 (m, 3 H), 7.61-7.78 (m, 7 H), 8.02-8.10 (m, 1 H), 8.53 (dd, J = 5.8, 2.8 Hz, 1 H), 9.35 (s, 1 H); MS m/z 493.2 (M + H)⁺  68

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indol-4-yl)phenyl]- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.76 (dd, J = 7.8, 2.8 Hz, 2 H), 0.98 (d, J = 4.5 Hz, 2 H), 1.41-1.75 (m, 2 H), 1.88-2.38 (m, 9 H), 2.41-2.66 (m, 1 H), 3.10-3.33 (m, 1 H), 3.60 (d, 3 H), 3.86-4.00 (m, 2 H), 6.68 (br. s., 1 H), 7.23 (d, 1 H), 7.30 (d, 1 H), 7.32 (d, J = 3.0 Hz, 1 H), 7.48 (d, J = 8.1 Hz, 1 H), 7.83 (d, J = 8.6 Hz, 2 H), 7.94 (d, J = 8.1 Hz, 2 H), 8.53 (br. s., 1 H); MS m/z 481.2 (M + H)⁺  69

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-isoquinolin-7-ylphenyl)- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.65- 0.80 (m, 2 H), 0.86-1.03 (m, 2 H), 1.43- 2.17 (m, 11 H), 2.28-2.55 (m, 1 H), 2.96- 3.58 (m, 3 H), 3.59-3.83 (m, 3 H), 7.70- 7.78 (m, 3 H), 7.83-7.91 (m, 2 H), 7.93- 8.04 (m, 2 H), 8.23 (s, 1 H), 8.58 (d, J = 6.1 Hz, 1 H), 9.37 (s, 1 H); MS m/z 493.2 (M + H)⁺  70

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[3′-(1H-pyrazol-3- yl)biphenyl-4-yl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (d, J = 6.6 Hz, 2 H), 0.90-1.04 (m, 2 H), 1.41- 1.76 (m, 2 H), 1.86-2.17 (m, 5 H), 2.17- 2.36 (m, 4 H), 2.38-2.70 (m, 1 H), 2.98- 3.64 (m, 3 H), 3.64-4.00 (m, 3 H), 6.83 (d, J = 2.5 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), 7.68 (d, J = 7.6 Hz, 1 H), 7.77 (d, J = 7.5 Hz, 1 H), 7.81-7.91 (m, 5 H), 7.96-8.05 (m, 1 H); MS m/z 508.3 (M + H)⁺  11

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-quinolin-6-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.57- 0.70 (m, 4 H), 1.35-1.70 (m, 2 H), 1.71- 2.14 (m, 26 H), 2.21-2.45 (m, 1 H), 2.83- 3.52 (m, 3 H), 3.52-3.67 (m, 1 H), 3.77 (t, J = 8.8 Hz, 2 H), 7.92 (dd, J = 8.1, 4.5 Hz, 1 H), 8.01 (t, J = 7.3 Hz, 2 H), 8.18 (dd, J = 7.8, 4.3 Hz, 2 H), 8.33-8.40 (m, 1 H), 8.41- 8.48 (m, 1 H), 8.69 (s, 1 H), 8.91 (d, J = 8.1 Hz, 1 H), 9.18 (d, J = 3.5 Hz, 1 H); MS m/z 493.3 (M + H)⁺  12

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 5.1 Hz, 4 H), 1.31-1.74 (m, 2 H), 1.74-2.16 (m, 9 H), 2.19-2.45 (m, 1 H), 2.82-3.51 (m,3 H), 3.52-3.67 (m, 1 H), 3.69-3.83 (m, 2 H), 8.05 (t, J = 8.1 Hz, 2 H), 8.24 (dd, J = 8.1, 5.1 Hz, 2 H), 8.47 (d, J = 8.6 Hz, 1 H), 8.53 (d, J = 6.6 Hz, 1 H), 8.67 (d, J = 9.1 Hz, 1 H), 8.73 (d, J = 6.6 Hz, 1 H), 8.80 (s, 1 H), 9.94 (s, 1 H); MS m/z 493.3 (M + H)⁺  13

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1-methyl-1H-pyrazol-4- yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 446.3 (M + H)⁺  72

2-[4-(1-Benzofuran-5-yl)-2-methylphenyl]- 3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.72- 0.85 (m, 2 H), 0.93-1.07 (m, 2 H), 1.42- 1.70 (m, 2 H), 1.84-2.35 (m, 9 H), 2.38- 2.61 (m, 1 H), 2.43 (s, 3 H), 2.98-3.26 (m, 1 H), 3.31-3.75 (m, 5 H), 6.86 (s, 1 H), 7.41-8.08 (m, 11 H); MS m/z 495.0 (M + H)⁺  73

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indol-5-yl)-2- methylphenyl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (d, J = 7.6 Hz, 2 H), 0.92-1.07 (m, 2 H), 1.42- 1.68 (m, 2 H), 1.83-2.17 (m, 5 H), 2.18- 2.38 (m, 4 H), 2.42 (s, 3 H), 2.44-2.61 (m, 1 H), 3.00-3.25 (m, 1 H), 3.30-3.75 (m, 5 H), 6.63 (br. s., 1 H), 7.29 (br. s., 1 H), 7.39-7.52 (m, 3 H), 7.61-7.70 (m, 2 H), 7.90 (s, 1 H), 8.45 (br. s., 1 H); MS m/z 495.0 (M + H)⁺  93

2-(4′-Chloro-3-methylbiphenyl-4-yl)-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.71- 0.85 (m, 2 H), 0.92-1.07 (m, 2 H), 1.39- 1.71 (m, 2 H), 1.82-2.31 (m, 8 H), 2.33- 2.59 (m, 1 H), 2.42 (s, 3 H), 2.95-3.27 (m, 1 H), 3.30-3.74 (m, 5 H), 7.43-7.52 (m, 3 H), 7.56 (d, J = 9.1 Hz, 4 H); MS m/z 489.9 (M + H)⁺  3

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-pyridin-4-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 443.2 (M + H)⁺  4

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.78 (dd, J = 7.6, 3.0 Hz, 2 H), 0.90-1.06 (m, 2 H), 1.39-1.76 (m, 2 H), 1.84-2.67 (m, 10 H), 3.06-3.78 (m, 4 H), 3.84-4.02 (m, 2 H), 6.64 (br. s., 1 H), 7.29 (br. s., 1 H), 7.41-7.52 (m, 2 H), 7.76-7.82 (m, 2 H), 7.83-7.90 (m, 2 H), 7.93 (s, 1 H), 8.51- 8.62 (m, 1 H); MS m/z 481.3 (M + H)⁺  5

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-pyridin-3-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 443.2 (M + H)⁺  22

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-quinolin-4-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 493.3 (M + H)⁺  82

2-(4′-Chlorobiphenyl-4-yl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70- 0.86 (m, 2 H), 0.98 (br. s., 2 H), 1.41-2.33 (m, 10 H), 2.35-2.64 (m, 1 H), 3.03-3.32 (m, 1 H), 3.32-3.63 (m, 2 H), 3.63-3.76 (m, 1 H), 3.77-3.94 (m, 2 H), 7.48 (d, 2 H), 7.58 (d, J = 8.6 Hz, 2 H), 7.80 (s, 4 H); MS m/z 476.1 (M + H)⁺  83

4′-(3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4-oxo-1,3-diazaspiro[4.4]non-1- en-2-yl)biphenyl-3-carbonitrile MS m/z 467.3 (M + H)⁺  84

N-[4′-(3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4-oxo-1,3-diazaspiro[4.4]non-1- en-2-yl)biphenyl-3-yl]methanesulfonamide ¹H NMR (400 MHz, CDCl₃) δ ppm 0.71- 0.85 (m, 2 H), 0.91-1.06 (m, 2 H), 1.45- 1.81 (m, 2 H), 1.92-2.18 (m, 5 H), 2.19- 2.46 (m, 4 H), 2.47-2.78 (m, 1 H), 3.01 (s, 3 H), 3.04-4.00 (m, 6 H), 7.16-7.24 (m, 2 H), 7.25-7.31 (m, 1 H), 7.32-7.42 (m, 1 H), 7.55-7.65 (m, 2 H), 7.78-7.89 (m, 2 H), 8.06 (br. s., 1 H); MS m/z 535.2 (M + H)⁺  85

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4′-methoxybiphenyl-4-yl)- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.68- 0.83 (m, 2 H), 0.92-1.03 (m, 2 H), 1.38- 1.72 (m, 2 H), 1.84-2.34 (m, 8 H), 2.35- 2.63 (m, 1 H), 3.05-3.31 (m, 1 H), 3.31- 3.75 (m, 3 H), 3.80-3.96 (m, 4 H), 7.03 (d, J = 8.6 Hz, 2 H), 7.60 (d, J = 8.6 Hz, 2 H), 7.78 (s, 4 H); MS m/z 472.2 (M + H)⁺  18

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(4-pyridin-2-ylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 443.3 (M + H)⁺ INT-E

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-phenyl-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 366.3 (M + H)⁺  33

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indol-6-yl)phenyl]- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.77 (dd, J = 7.6, 2.5 Hz, 2 H), 0.91-1.03 (m, 2 H), 1.41-1.72 (m, 2 H), 1.88-2.36 (m, 9 H), 2.39-2.63 (m, 1 H), 3.28 (dd, J = 10.1, 7.6 Hz, 1 H), 3.32-3.75 (m, 3 H), 3.83- 3.96 (m, 2 H), 6.61 (br. s., 1 H), 7.32 (t, J = 2.8 Hz, 1 H), 7.39 (d, J = 9.1 Hz, 1 H), 7.65 (s, 1 H), 7.74 (d, J = 8.6 Hz, 1 H), 7.76- 7.81 (m, 2 H), 7.82-7.88 (m, 2 H), 8.60- 8.70 (m, 1 H); MS m/z 481.2 (M + H)⁺  34

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1-methyl-1H-indazol-6- yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.72- 0.84 (m, 2 H), 0.94-1.04 (m, 2 H), 1.41- 1.76 (m, 2 H), 1.86-2.36 (m, 9 H), 2.38- 2.67 (m, 1 H), 3.06-3.34 (m, 1 H), 3.34- 3.65 (m, 2 H), 3.65-3.77 (m, 1 H), 3.80- 4.01 (m, 2 H), 4.18 (s, 3 H), 7.44 (d, J = 8.1 Hz, 1 H), 7.64 (s, 1 H), 7.82-7.88 (m, 3 H), 7.89-7.95 (m, 2 H), 8.07 (s, 1 H); MS m/z 496.4 (M + H)⁺  35

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70- 0.83 (m, 2 H), 0.93-1.04 (m, 2 H), 1.40- 1.75 (m, 2 H), 1.87-2.36 (m, 9 H), 2.38- 2.67 (m, 1 H), 3.06-3.33 (m, 1 H), 3.33- 3.76 (m, 3 H), 3.81-3.98 (m, 2 H), 4.13 (s, 3 H), 7.53 (d, J = 9.1 Hz, 1 H), 7.70 (d, J = 9.1 Hz, 1 H), 7.83 (d, 2 H), 7.88 (d, 2 H), 8.01 (s, 1 H), 8.10 (s, 1 H); MS m/z 496.4 (M + H)⁺  91

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4′-(2H-tetrazol-5- yl)biphenyl-4-yl]-1,3-diazaspiro[4.4]non-1- en-4-one MS m/z 509.9 (M + H)⁺  92

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indazol-4-yl)phenyl]- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.65- 0.79 (m, 2 H), 0.87-1.03 (m, 2 H), 1.43- 1.73 (m, 2 H), 1.81-2.01 (m, 4 H), 2.02- 2.20 (m, 5 H), 2.34-2.59 (m, 1 H), 3.02- 3.30 (m, 1 H), 3.30-3.85 (m, 5 H), 7.27- 7.32 (m, 1 H), 7.43-7.52 (m, 1 H), 7.52- 7.59 (m, 1 H), 7.69-7.79 (m, 2 H), 7.79- 7.89 (m, 2 H), 8.19 (br. s., 1 H); MS m/z 482.0 (M + H)⁺  94

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-(2′,4′-dichloro-3- methylbiphenyl-4-yl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.63- 0.83 (m, 2 H), 0.85-1.05 (m, 2 H), 1.38- 1.71 (m, 2 H), 1.74-2.19 (m, 9 H), 2.37 (s, 3 H), 2.39-2.52 (m, 1 H), 2.95-3.24 (m, 1 H), 3.25-3.41 (m, 1 H), 3.43-3.71 (m, 4 H), 7.27-7.31 (m, 1 H), 7.31-7.43 (m, 4 H), 7.52 (s, 1 H); MS m/z 523.8 (M + H)⁺  39

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.76 (m, 2 H), 0.84-0.96 (m, 2 H), 1.19- 1.37 (m, 2 H), 1.73-1.83 (m, 2 H), 1.83- 1.93 (m, 2 H), 2.77-2.94 (m, 1 H), 3.61 (dd, J = 9.8, 5.6 Hz, 1 H), 3.91-4.04 (m, 2 H), 4.04-4.11 (m, 1 H), 4.14 (s, 3 H), 4.24 (t, J = 8.2 Hz, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.63-7.74 (m, 3 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.99 (s, 1 H), 8.07 (s, 1 H); MS m/z 454 (M + H)⁺ m.p. 191.8° C.  38

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one 1H NMR (300 MHz, CDCl₃) δ ppm 0.64- 0.74 (m, 2 H), 0.87-0.94 (m, 2 H), 1.23- 1.36 (m, 2 H), 1.75-1.84 (m, 2 H), 1.84- 1.93 (m, 2 H), 2.79-2.94 (m, 1 H), 3.61 (dd, J = 9.8, 5.6 Hz, 1 H), 3.90-4.04 (m, 2 H), 4.04-4.14 (m, 1 H), 4.16 (s, 3 H), 4.25 (t, J = 8.3 Hz, 1 H), 7.44 (dd, J = 8.4, 1.2 Hz, 1 H), 7.62 (s, 1 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.80-7.88 (m, 3 H), 8.04 (s, 1 H); MS m/z 454 (M + H)⁺ m.p. 174.6° C.  51

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.75 (m, 2 H), 0.87-0.97 (m, 2 H), 1.23- 1.37 (m, 1 H), 1.74-1.84 (m, 2 H), 1.84- 1.93 (m, 2 H), 2.76-2.96 (m, 1 H), 3.62 (dd, J = 9.8, 5.6 Hz, 1 H), 3.90-4.16 (m, 4 H), 4.25 (t, J = 8.3 Hz, 1 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.64-7.72 (m, 3 H), 7.79 (d, J = 8.4 Hz, 2 H), 8.02 (s, 1 H), 8.16 (s, 1 H), 10.39 (br. s., 1 H); MS m/z 440 (M + H)⁺ m.p. >300° C.  40

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.77 (m, 2 H), 0.83-1.01 (m, 2 H), 1.22- 1.37 (m, 1 H), 1.73-1.83 (m, 2 H), 1.83- 1.92 (m, 2 H), 2.73-2.97 (m, 1 H), 3.63 (dd, J = 9.9, 5.6 Hz, 1 H), 3.88-4.16 (m, 4 H), 4.23 (t, J = 8.2 Hz, 1 H), 6.58-6.69 (m, 1 H), 7.29 (d, J = 2.9 Hz, 1 H), 7.44-7.52 (m, 2 H), 7.64 (d, J = 8.2 Hz, 2 H), 7.80 (d, J = 8.2 Hz, 2 H), 7.92 (s, 1 H), 8.43 (br. s., 1 H); MS m/z 439 (M + H)⁺ m.p. 190.8° C.  43

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-pyrazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 404 (M + H)⁺ m.p. 164.9° C.  42

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-pyrazol-4- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 404 (M + H)⁺ m.p. 164.7° C.  41

4′-(6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept-4- en-5-yl)biphenyl-4-carbonitrile 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.76 (m, 2 H), 0.85-0.96 (m, 2 H), 1.23- 1.36 (m, 1 H), 1.74-1.83 (m, 2 H), 1.83- 1.94 (m, 2 H), 2.70-2.95 (m, 1 H), 3.57 (dd, J = 9.9, 5.6 Hz, 1 H), 3.87-4.02 (m, 3 H), 4.02-4.16 (m, 1 H), 4.24 (t, J = 8.3 Hz, 1 H), 7.65-7.85 (m, 8 H); MS m/z 425 (M + H)⁺ m.p. 182.8° C.  52

5-[4-(1,3-Benzoxazol-5-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.65- 0.78 (m, 2 H), 0.91 (t, J = 3.7 Hz, 2 H), 1.23- 1.35 (m, 1 H), 1.75-1.84 (m, 2 H), 1.88 (quin, J = 3.5 Hz, 2 H), 2.77-2.95 (m, 1 H), 3.62 (dd, J = 9.9, 5.6 Hz, 1 H), 3.88-4.16 (m, 4 H), 4.25 (t, J = 8.2 Hz, 1 H), 7.64- 7.75 (m, 4 H), 7.79 (d, J = 8.4 Hz, 2 H), 8.05 (s, 1 H), 8.17 (s, 1 H); MS m/z 441 (M + H)⁺  53

5-(3′-Amino-4′-hydroxybiphenyl-4-yl)-6-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)⁺  54

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-4-hydroxybiphenyl-3- yl]formamide MS m/z 431 (M + H)⁺  50

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.65- 0.80 (m, 2 H), 0.89-1.01 (m, 2 H), 1.23- 1.38 (m, 1 H), 1.73-1.84 (m, 2 H), 1.84- 1.95 (m, 2 H), 2.75-2.96 (m, 1 H), 3.61 (dd, J = 10.0, 5.7 Hz, 1 H), 3.84-4.15 (m, 4 H), 4.27 (t, J = 8.5 Hz, 1 H), 6.82 (d, J = 8.5 Hz, 2 H), 7.41 (d, J = 8.5 Hz, 2 H), 7.52- 7.65 (m, 4 H), 7.67 (s, 1 H); MS m/z 416 (M + H)⁺ 120

2-[4-(1-Benzofuran-5-yl)-2-fluorophenyl]-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.76 (d, J = 8.1 Hz, 2 H), 0.90-1.07 (m, 2 H), 1.41- 1.73 (m, 2 H), 1.81-2.26 (m, 9 H), 2.35- 2.63 (m, 1 H), 2.97-3.28 (m, 1 H), 3.28- 3.79 (m, 5 H), 6.87 (s, 1 H), 7.48-7.59 (m, 2 H), 7.63 (d, J = 8.6 Hz, 2 H), 7.68-7.80 (m, 2 H), 7.86 (s, 1 H); MS m/z 499.9 (M + H)⁺ 121

2-(4′-Chloro-3-fluorobiphenyl-4-yl)-3- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70- 0.89 (m, 2 H), 0.90-1.11 (m, 2 H), 1.39- 1.72 (m, 2 H), 1.81-2.28 (m, 9 H), 2.34- 2.62 (m, 1 H), 2.95-3.28 (m, 1 H), 3.29- 3.77 (m, 5 H), 7.42-7.52 (m, 3 H), 7.56 (d, J = 8.6 Hz, 3 H), 7.73 (t, J = 7.6 Hz, 1 H); MS m/z 493.9 (M + H)⁺ 156

2-[4-(1-Benzofuran-5-yl)-2- methoxyphenyl]-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.67- 0.84 (m, 2 H), 0.90-1.02 (m, 2 H), 1.38- 1.66 (m, 2 H), 1.81-2.64 (m, 10 H), 2.98- 3.22 (m, 1 H), 3.28-3.78 (m, 5 H), 4.00 (s, 3 H), 6.86 (d, 1 H), 7.24-7.30 (m, 1 H), 7.40 (d, J = 7.6 Hz, 1 H), 7.51-7.58 (m, 1 H), 7.62 (d, 1 H), 7.65-7.76 (m, 2 H), 7.85 (s, 1 H); MS m/z 511.9 (M + H)⁺ 157

3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-2-[4-(1H-indol-5-yl)-2- methoxyphenyl]-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.67- 0.82 (m, 2 H), 0.89-1.03 (m, 2 H), 1.38- 1.64 (m, 2 H), 1.82-2.63 (m, 10 H), 2.99- 3.20 (m, 1 H), 3.26-3.85 (m, 5 H), 3.93- 4.04 (m, 3 H), 6.64 (br. s., 1 H), 7.29 (d, J = 7.1 Hz, 2 H), 7.34-7.44 (m, 2 H), 7.44- 7.51 (m, 1 H), 7.61-7.71 (m, 1 H), 7.89 (s, 1 H), 8.48-8.64 (m, 1 H); MS m/z 511.0 (M + H)⁺ 178

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-1-benzofuran-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.73 (m, 2 H), 0.80-0.99 (m, 2 H), 1.24- 1.38 (m, 2 H), 1.74-1.82 (m, 2 H), 1.82- 1.93 (m, 2 H), 2.50 (s, 3 H), 2.73-2.94 (m, 1 H), 3.62 (dd, J = 9.6, 5.6 Hz, 1 H), 3.85- 4.15 (m, 3 H), 4.23 (t, J = 8.2 Hz, 1 H), 6.44 (s, 1 H), 7.40-7.55 (m, 2 H), 7.65 (d, J = 8.1 Hz, 2 H), 7.72 (s, 1 H), 7.77 (d, J = 8.2 Hz, 2 H); MS m/z 454 (M + H)⁺ m.p. 166.3° C. 179

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.78 (m, 2 H), 0.85-1.01 (m, 2 H), 1.27- 1.40 (m, 1 H), 1.70-1.82 (m, 2 H), 1.82- 1.95 (m, 2 H), 2.34 (s, 3 H), 2.50 (s, 3 H), 2.75-3.02 (m, 1 H), 3.63 (dd, J = 8.6, 5.6 Hz, 1 H), 3.86-4.16 (m, 4 H), 4.25 (t, J = 7.9 Hz, 1 H), 6.41 (s, 1 H), 7.15 (d, J = 8.1 Hz, 1 H), 7.33-7.64 (m, 5 Hz); MS m/z 468 (M + H)⁺ m.p. 170.1° C. 180

5-[4-(1-Benzofuran-5-yl)-3-methylphenyl]- 6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.78 (m, 2 H), 0.92-1.02 (m, 2 H), 1.40- 2.11 (m, 7 H), 2.34 (s, 3 H), 2.39-2.71 (m, 1 H), 2.96-3.98 (m, 6 H), 6.82 (s, 1 H), 7.18-7.31 (m, 1 H), 7.35-7.48 (m, 2 H), 7.49-7.61 (m, 3 H), 7.69 (s, 1 H); MS m/z 468 (M + H)⁺ m.p. 71.9° C.

Example 2 R)-5-(4-(Benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (Compound #58

STEP A: (R)-Cyclopropyl-(3-(hydroxymethyl)pyrrolidin-1-yl)methanone

To a solution of (R)-pyrrolidin-3-ylmethanol (3.45 g, 25.07 mmol) and DIPEA (8.50 mL, 50 mmol) in DCM (100 mL) was added at 0° C. cyclopropanecarbonyl chloride (2.27 mL, 25.1 mmol). After stirring for 5 h at room temperature, the reaction mixture was partitioned between DCM and aqueous 1.0M NaOH (100 mL) and water (50 mL). The organic phase was washed with brine, dried over MgSO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 0 to 10% MeOH/DCM) to yield (R)-cyclopropyl(3-(hydroxymethyl)pyrrolidin-1-yl)methanone (2.53 g, 60%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.84 (m, 2H), 0.89-1.09 (m, 2H), 1.42-2.69 (m, 5H), 3.24 (dd, J=12.1, 7.1 Hz, 0.5H), 3.34-3.52 (m, 1H), 3.52-3.89 (m, 4.5H); MS m/z 170 (M+H)⁺.

STEP B: (R)-(1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl methanesulfonate

To a solution of (R)-cyclopropyl(3-(hydroxymethyl)pyrrolidin-1-yl)methanone (2.53 g, 14.95 mmol) and triethylamine (4.17 mL, 29.9 mmol) in DCM (70 mL) was added at 0° C. methanesulfonyl chloride (1.39 mL, 17.9 mmol). After stirring overnight at room temperature, the reaction mixture was partitioned between DCM (100 mL) and water (50 mL). The organic phase was washed with brine, dried over MgSO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 0 to 10% MeOH/DCM) to yield (R)-(1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl methanesulfonate (3.41 g, 92%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.88 (m, 2H), 0.87-1.11 (m, 2H), 1.50-2.31 (m, 3H), 2.53-2.88 (m, 1H), 3.03 (s, 1.5H), 3.05 (s, 1.5H), 3.20-3.37 (m, 0.5H), 3.38-3.56 (m, 1H), 3.57-3.96 (m, 2.5H), 4.05-4.39 (m, 2H); MS m/z 248 (M+H)⁺.

STEP C: ((R)-5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a stirring solution of 5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (1.53 g, 5.77 mmol) and (R)-(1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl methanesulfonate (1.43 g, 5.77 mmol) in DMF (25 mL) was added Cs₂CO₃ (3.76 g, 11.5 mmol). After stirring at room temperature for 6 h at 65° C., the reaction mixture was filtered through a pad of diatomaceous earth and further washed with EtOAc (3×20 ml). The filtrate was concentrated and the residue was partitioned between EtOAc and water. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 100% EtOAc and then 0-10% MeOH/DCM) to yield (R)-5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (1 g, 40%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.82 (m, 2H), 0.86-1.05 (m, 2H), 1.38-2.07 (m, 7H), 2.27-2.57 (m, 1H), 2.93-3.08 (m, 0.5H), 3.16-3.39 (m, 1H), 3.44-3.84 (m, 4.5H), 7.41-7.54 (m, 2H), 7.62-7.73 (m, 2H); MS m/z 416 (M+H)⁺.

STEP D: (R)-5-(4-(Benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a solution of (R)-5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (104 mg, 0.25 mmol) in acetonitrile (2 mL) was added 2-(benzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (73.23 mg, 0.3 mmol), aqueous 1.0M Na₂CO₃ (0.5 mL, 0.5 mmol) and Bis(triphenylphosphine)palladium(II) chloride (9.12 mg, 0.013 mmol). The reaction mixture was bubbled with nitrogen for 5 min and heated to 85° C. for 2 h under nitrogen atmosphere. The resulting mixture was diluted with DCM and the organic layer was filtered and concentrated to yield a residue which was purified by flash chromatography (silica gel, 0-10% MeOH/DCM) and re-purified by reverse phase prep-HPLC to yield (R)-5-(4-(benzofuran-5-yl)phenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (20 mg, 17%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.79 (m, 2H), 0.88-1.01 (m, 2H), 1.39-2.08 (m, 8H), 2.33-2.68 (m, 1H), 2.97-3.17 (m, 0.5H), 3.18-3.43 (m, 1H), 3.45-3.94 (m, 4.5H), 6.85 (d, J=1.8 Hz, 1H), 7.51-7.64 (m, 2H), 7.64-7.73 (m, 3H), 7.73-7.81 (m, 2H), 7.85 (s, 1H); MS m/z 454.0 (M+H)⁺.

Following the procedure described in Example 2, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  10

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.59- 0.82 (m, 2 H), 0.87-0.97 (m, 2 H), 0.97-1.17 (m, 2 H), 1.52-1.92 (m, 9 H), 2.34-2.65 (m, 1 H), 2.82-3.11 (m, 1 H), 3.60-3.76 (m, 1 H), 4.15 (d, J = 12.1 Hz, 1 H), 4.53 (d, J = 11.4 Hz, 1 H), 6.63 (t, J = 2.3 Hz, 1 H), 7.26 (d, J = 2.9 Hz, 1 H), 7.41-7.55 (m, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.79 (d, J = 8.4 Hz, 2 H), 7.93 (s, 1 H), 8.63 (br. s., 1 H); MS m/z 467 (M + H)⁺ m.p. 129.4° C.  9

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1-methyl-1H-pyrazol-4- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 432 (M + H)⁺ m.p. 144.5° C.  8

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1-methyl-1H-pyrazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z (M + H)⁺ m.p. 75.9° C.  7

4′-(6-{[1-(Cyclopropylcarbonyl)piperidin- 4-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 4-carbonitrile MS m/z 453 (M + H)⁺ m.p. 154.5° C.  6

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4-pyridin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 429 (M + H)⁺ m.p. 132.0° C.  20

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4-isoquinolin-6-ylphenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.65- 0.76 (m, 2 H), 0.88-0.95 (m, 2 H), 0.95-1.23 (m, 2 H), 1.48-1.75 (m, 4 H), 1.75-1.83 (m, 2 H), 1.83-1.99 (m, 3 H), 2.48 (t, J = 11.5 Hz, 1 H), 2.99 (t, J = 12.1 Hz, 1 H), 3.69 (dd, J = 14.2, 6.9 Hz, 2 H), 4.16 (d, J = 11.8 Hz, 1 H), 4.53 (d, J = 12.1 Hz, 1 H), 7.68-7.79 (m, 3 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.91 (dd, J = 8.6, 1.7 Hz, 1 H), 8.04-8.16 (m, 2 H), 8.60 (d, J = 5.8 Hz, 1 H), 9.32 (s, 1 H); MS m/z 479 (M + H)⁺ m.p. 97.9° C.  19

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)⁺ m.p. 107.7° C.  24

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1-methyl-1H-indazol-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)⁺ m.p. 104.0° C.  29

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.77 (m, 2 H), 0.89-0.97 (m, 2 H), 1.06 (d, J = 19.0 Hz, 2 H), 1.51-1.73 (m, 3 H), 1.75-1.94 (m, 6 H), 2.49 (t, J = 11.3 Hz, 1 H), 2.99 (t, J = 11.8 Hz, 1 H), 3.55-3.82 (m, 2 H), 4.16 (d, J = 12.5 Hz, 1 H), 4.54 (d, J = 11.7 Hz, 1 H), 7.58 (m, J = 8.7 Hz, 1 H), 7.63-7.73 (m, 3 H), 7.77 (m, J = 8.2 Hz, 2 H), 8.02 (s, 1 H), 8.16 (br. s., 1 H); MS m/z 468 (M + H)⁺ m.p. 179.9° C.  25

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4-isoquinolin-7-ylphenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 479 (M + H)⁺ m.p. 151.1° C.  30

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4-isoquinolin-7-ylphenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.60- 0.78 (m, 2 H), 0.87-1.03 (m, 2 H), 1.42-2.08 (m, 7.5 H), 2.33-2.50 (m, 0.5 H), 2.51-2.68 (m, 0.5 H), 3.05 (dd, J = 12.0, 7.2 Hz, 0.5 H), 3.17-3.44 (m, 1 H), 3.49-3.89 (m, 4 H), 7.66-7.80 (m, 3 H), 7.83-7.92 (m, 2 H), 7.92-8.05 (m, 2 H), 8.23 (s, 1 H), 8.59 (br. s., 1 H), 9.37 (br. s., 1 H); MS m/z 465 (M + H)⁺ m.p. 92.3° C.  28

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61- 0.79 (m, 2 H), 0.84-1.05 (m, 2 H), 1.38-2.09 (m, 8 H), 2.37-2.51 (m, 0.5 H), 2.52-2.67 (m, 0.5 H), 3.06 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.22-3.39 (m, 1 H), 3.47-3.92 (m, 4.5 H), 4.13 (s, 3 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.63-7.73 (m, 3 H), 7.73-7.83 (m, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H); MS m/z 468 (M + H)⁺ m.p. 169.6° C.  27

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.57- 0.81 (m, 2 H), 0.83-1.05 (m, 2 H), 1.38-2.12 (m, 8 H), 2.34-2.50 (m, 0.5 H), 2.51-2.69 (m, 0.5 H), 2.97-3.14 (m, 0.5 H), 3.18-3.43 (m, 1 H), 3.43- 3.97 (m, 4.5 H), 4.15 (s, 3 H), 7.43 (d, J = 8.0 Hz, 1 H), 7.61 (br. s., 1 H), 7.65- 7.77 (m, 2 H), 7.77-7.93 (m, 3 H), 8.03 (br. s., 1 H); MS m/z 468 (M + H)⁺ m.p. 138.2° C.  31

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1H-indol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.83 (m, 2 H), 0.83-1.07 (m, 2 H), 1.39-2.09 (m, 8 H), 2.32-2.65 (m, 1 H), 3.09 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.19-3.41 (m, 1 H), 3.42-3.97 (m, 4.5 H), 6.62 (br. s., 1 H), 7.27 (s, 1 H), 7.46 (d, J = 3.0 Hz, 2 H), 7.65 (dd, J = 8.0, 4.2 Hz, 2 H), 7.73-7.84 (m, 2 H), 7.91 (s, 1 H), 8.65 (br. s., 1 H); MS m/z 453 (M + H)⁺ m.p. 178.2° C.  47

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4-isoquinolin-6-ylphenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.78 (m, 2 H), 0.87-1.01 (m, 2 H), 1.41-1.58 (m, 1.5 H), 1.65-2.10 (m, 5.5 H), 2.35-2.69 (m, 1 H), 3.05 (dd, J = 12.0, 7.2 Hz, 1 H), 3.23-3.41 (m, 0.5 H), 3.49-3.89 (m, 4.5 H), 7.70-7.80 (m, 3 H), 7.84-7.94 (m, 3 H), 8.07 (s, 1 H), 8.11 (d, J = 8.5 Hz, 1 H), 8.60 (d, J = 5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 465 (M + H)⁺ m.p. 162.3° C.  64

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.68- 0.83 (m, 2 H), 0.92-1.07 (m, 2 H), 1.38-2.16 (m, 7 H), 2.34-2.72 (m, 1 H), 3.05 (dd, J = 12.0, 7.2 Hz, 0.5 H), 3.17-3.99 (m, 5.5 H), 6.72-6.93 (m, 2 H), 7.32-7.50 (m, 2 H), 7.54-7.74 (m, 4 H), 7.80-8.25 (m, 1 H); MS m/z 430 (M + H)⁺  48

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 4-carbonitrile ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.77 (m, 2 H), 0.89-1.00 (m, 2 H), 1.42-1.56 (m, 1.5 H), 1.64-2.11 (m, 5.5 H), 2.31-2.67 (m, 1 H), 3.02 (dd, J = 12.1, 7.3 Hz, 0.5 H), 3.22-3.39 (m, 1 H), 3.44-3.92 (m, 4.5 H), 7.67-7.89 (m, 8 H); MS m/z 439 (M + H)⁺ m.p. 90.7° C.  32

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4-pyridin-4-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 429 (M + H)⁺ m.p. >300° C.  26

5-[4-(1H-Benzimidazol-5-yl)phenyl]-6- {[1-(cyclopropylcarbonyl)piperidin-4- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.56- 1.40 (m, 8 H), 1.45-2.01 (m, 6 H), 2.39-2.62 (m, 1 H), 2.84-3.13 (m, 1 H), 3.55-3.82 (m, 3 H), 4.05-4.27 (m, 1 H), 4.41-4.62 (m, 1 H), 7.42-7.94 (m, 8 H), 8.13 (br. s., 1 H); MS m/z 468 (M + H)⁺ m.p. 144° C.  37

5-[4-(1,3-Benzoxazol-5-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)piperidin-4- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 469 (M + H)⁺  55

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. 161.7° C.  57

5-[4-(1,3-Benzothiazol-5-yl)phenyl]-6- {[1-(cyclopropylcarbonyl)piperidin-4- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.41- 0.73 (m, 2 H), 0.79-0.89 (m, 1 H), 1.39-1.90 (m, 9 H), 2.23-2.53 (m, 1 H), 2.76-3.06 (m, 1 H), 3.22-3.49 (m, 2 H), 3.49-3.80 (m, 3 H), 3.93-4.24 (m, 1 H), 4.24-4.60 (m, 1 H), 7.53- 7.85 (m, 5 H), 8.00 (d, J = 8.0 Hz, 1 H), 8.34 (br. s., 1 H), 9.00 (br. s., 1 H); MS m/z 485 (M + H)⁺ m.p. 152.6° C.  71

5-[4-(1,3-Benzothiazol-5-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.47-0.76 (m, 4 H), 1.29-1.67 (m, 4.5 H), 1.67-1.82 (m, 2 H), 1.82-1.97 (m, 1 H), 2.18-2.45 (m, 1 H), 2.90 (dd, J = 11.5, 6.8 Hz, 0.5 H), 3.05-3.28 (m, 2 H), 3.40-3.63 (m, 2 H), 3.68-3.85 (m, 2 H), 7.78-7.86 (m, 1 H), 7.90 (d, J = 8.2 Hz, 1 H), 7.99 (d, J = 7.1 Hz, 2 H), 8.30 (d, J = 8.2 Hz, 1 H), 8.46 (br. s., 1 H), 9.47 (s, 1 H) MS m/z 471 (M + H)⁺ m.p. 82.7° C. 105

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-fluorobiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.66- 0.75 (m, 2 H), 0.90-0.98 (m, 2 H), 1.41-1.59 (m, 2 H), 1.65-2.08 (m, 5 H), 2.31-2.67 (m, 1 H), 3.04 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.21-3.38 (m, 1 H), 3.50-3.90 (m, 4.5 H), 7.18 (t, J = 8.7 Hz, 2 H), 7.56-7.64 (m, 2 H), 7.64- 7.75 (m, 4 H); MS m/z 432 (M + H)⁺ m.p. 153.7° C. 104

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′- (trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)⁺ m.p. 253.8° C. 115

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(3′-hydroxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61- 0.88 (m, 2 H), 0.89-1.13 (m, 2 H), 1.39-2.18 (m, 7 H), 2.34-2.71 (m, 1 H), 2.96-4.20 (m, 6 H), 6.64-6.98 (m, 2 H), 6.97-7.18 (m, 1 H), 7.18-7.41 (m, 1 H), 7.45-7.87 (m, 4 H), 8.07- 8.57 (m, 1 H); MS m/z 430 (M + H)⁺ m.p. >300° C. 103

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-methoxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.75 (m, 2 H), 0.88-0.98 (m, 2 H), 1.41-1.57 (m, 2 H), 1.62-2.01 (m, 6 H), 2.32-2.63 (m, 0.5 H), 3.18-3.37 (m, 1 H), 3.49-3.86 (m, 4.5 H), 3.87 (s, 3 H), 7.01 (d, J = 8.7 Hz, 2 H), 7.57 (d, J = 8.7 Hz, 2 H), 7.64 (dd, J = 8.4, 1.9 Hz, 2 H), 7.69 (dd, J = 8.4, 3.8 Hz, 2 H); MS m/z 444 (M + H)⁺ m.p. 76.6° C. 102

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(3′-fluorobiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.78 (m, 2 H), 0.86-1.02 (m, 2 H), 1.41-2.08 (m, 7 H), 2.33-2.65 (m, 1 H), 3.04 (dd, J = 12.1, 7.1 Hz, 0.5 H), 3.20-3.39 (m, 1 H), 3.50-3.90 (m, 4.5 H), 7.05-7.16 (m, 1 H), 7.30-7.38 (m, 1 H), 7.38-7.51 (m, 2 H), 7.65-7.78 (m, 4 H); MS m/z 432 (M + H)⁺ m.p. 131.1° C. 101

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(3′-methylbiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (dd, J = 7.7, 3.0 Hz, 2 H), 0.87-1.02 (m, 2 H), 1.42-2.08 (m, 7 H), 2.35-2.62 (m, 1 H), 2.45 (s, 3 H), 3.06 (dd, J = 12.0, 7.0 Hz, 0.5 H), 3.20-3.39 (m, 1 H), 3.43-3.90 (m, 4.55 H), 7.23 (d, J = 7.0 Hz, 1 H), 7.33-7.51 (m, 3 H), 7.63-7.70 (m, 2 H), 7.70-7.79 (m, 2 H); MS m/z 428 (M + H)⁺ m.p. >300° C. 100

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-methylbiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.78 (m, 2 H), 0.90-1.00 (m, 2 H), 1.38-2.10 (m, 7 H), 2.35-2.69 (m, 1 H), 2.41-2.44 (m, 3 H), 3.06 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.14-3.41 (m, 1 H), 3.40-3.93 (m, 4.5 H), 7.29 (d, J = 8.1 Hz, 2 H), 7.54 (d, J = 8.1 Hz, 2 H), 7.61-7.69 (m, 2 H), 7.69-7.78 (m, 2 H); MS m/z 428 (M + H)⁺ m.p. 123.3° C. 114

5-(4′-Chlorobiphenyl-4-yl)-6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.81 (m, 2 H), 0.86-1.04 (m, 2 H), 1.38-2.10 (m, 7 H), 2.30-2.66 (m, 1 H), 3.04 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.18-3.41 (m, 1 H), 3.42-3.93 (m, 4.5 H), 7.45 (d, J = 8.1 Hz, 2 H), 7.57 (d, J = 8.5 Hz, 2 H), 7.63-7.80 (m, 4 H); MS m/z 448 (M + H)⁺ 113

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(3′-methoxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.60- 0.82 (m, 2 H), 0.83-1.04 (m, 2 H), 1.37-2.10 (m, 7 H), 2.26-2.67 (m, 1 H), 2.91-3.87 (m, 6 H), 3.89 (s, 3 H), 6.95 (d, J = 8.0 Hz, 1 H), 7.11-7.26 (m, 2 H), 7.40 (t, J = 7.8 Hz, 1 H), 7.56-7.86 (m, 4 H); MS m/z 444 (M + H)⁺ 112

5-(3′-Chlorobiphenyl-4-yl)-6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.78 (m, 2 H), 0.86-1.04 (m, 2 H), 1.38-2.09 (m, 7 H), 2.31-2.66 (m, 1 H), 3.04 (dd, J = 12.0, 7.0 Hz, 0.5 H), 3.17-3.40 (m, 1 H), 3.50-3.91 (m, 4.5 H), 7.34-7.47 (m, 2 H), 7.47-7.56 (m, 1 H), 7.62 (s, 1 H), 7.65-7.78 (m, 4 H); MS m/z 448 (M + H)⁺ m.p. 129.4° C. 123

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)biphenyl- 3-carbonitrile ms m/z 439 (M + H)⁺ m.p. 171.4° C. 145

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′- (dimethylamino)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.56-0.70 (m, 4 H), 1.31-1.67 (m, 4 H), 1.67-1.94 (m, 3 H), 2.16-2.45 (m, 1 H), 2.89 (dd, J = 11.8, 6.9 Hz, 0.5 H), 2.97 (s, 6 H), 3.06-3.30 (m, 1.5 H), 3.37-3.65 (m, 2 H), 3.74 (t, J = 7.1 Hz, 2 H), 6.78 (dd, J = 8.1, 1.8 Hz, 1 H), 6.95- 7.04 (m, 2 H), 7.30 (m, J = 8.1, 8.1 Hz, 1 H), 7.71-7.79 (m, 2 H), 7.79-7.88 (m, 2 H); MS m/z 457 (M + H)⁺ m.p. 74.0° C. 124

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′- (dimethylamino)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.2 Hz, 4 H), 1.47-1.66 (m, 4 H), 1.67-1.94 (m, 3 H), 2.16-2.44 (m, 1 H), 2.89 (dd, J = 11.8, 6.9 Hz, 0.5 H), 2.96 (s, 6 H), 3.06-3.30 (m, 2 H), 3.36-3.60 (m, 1.5 H), 3.74 (t, J = 6.7 Hz, 2 H), 6.82 (d, J = 8.7 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.66-7.80 (m, 4 H); MS m/z 457 (M + H)⁺ m.p. 274.9° C. 125

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′- (trifluoromethoxy)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)⁺ m.p. 146.2° C. 126

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′- (trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.62- 0.80 (m, 2 H), 0.88-1.04 (m, 2 H), 1.39-1.60 (m, 2 H), 1.73-2.12 (m, 5 H), 2.31-2.67 (m, 1 H), 3.04 (dd, J = 11.8, 7.1 Hz, 0.5 H), 3.19-3.40 (m, 1 H), 3.40-3.94 (m, 4.5 H), 7.55-7.95 (m, 8 H); MS m/z 482 (M + H)⁺ m.p. 120.5° C. 146

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′- (trifluoromethoxy)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)⁺ m.p. 76.3° C. 111

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(3′-methylbiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 442 (M + H)⁺ m.p. 101.9° C.  97

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-methylbiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 442 (M + H)⁺ m.p. 167.1° C.  99

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-methoxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 458 (M + H)⁺ m.p. >300° C.  98

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(2′-methoxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 458 (M + H)⁺ m.p. >300° C. 110

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-fluorobiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 446 (M + H)⁺ m.p. 169.9° C. 109

5-(4′-Chlorobiphenyl-4-yl)-6-{[1- (cyclopropylcarbonyl)piperidin-4- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 462 (M + H)⁺ m.p. 196.8° C.  55

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. 153.1° C. 108

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(3′-hydroxybiphenyl-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)⁺ m.p. >300° C. 107

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4′- (trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)⁺ m.p. 187.7° C. 158

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(3′-fluorobiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 446 (M + H)⁺

Example 3 (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one (Compound #65)

STEP A: (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one (Compound #64)

(R)-5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (0.465 g, 1.117 mmol), (4-hydroxyphenyl)boronic acid (0.2 g, 1.45 mmol), tetrakis(triphenylphosphine) palladium (0.063 g, 0.055 mmol), aqueous 1.0M sodium carbonate (2.23 mL, 2.23 mmol) and 1,4-dioxane (5 mL) were combined and bubbled with nitrogen for 5 min. The resulting mixture was heated to reflux under nitrogen for 3 h. The resulting mixture was diluted with DCM (30 mL), dried over MgSO₄, filtered and concentrated in vacuo to yield a residue which was purified by flash chromatography (silica gel 0-10% MeOH in DCM) to yield (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-hydroxyl[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one (175 mg, 36%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.68-0.83 (m, 2H), 0.92-1.07 (m, 2H), 1.38-2.16 (m, 7H), 2.34-2.72 (m, 1H), 3.05 (dd, J=12.0, 7.2 Hz, 0.5H), 3.17-3.99 (m, 5.5H), 6.72-6.93 (m, 2H), 7.32-7.50 (m, 2H), 7.54-7.74 (m, 4H), 7.80-8.25 (m, 1H); MS m/z 430.0 (M+H)⁺.

STEP B: (R)-4′-(6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl]-4-yl trifluoromethanesulfonate

To a solution of (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-((4′-hydroxy-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one (175 mg, 0.407 mmol) in DCM (5 mL) and pyridine (1 mL) was added at 0° C. trifluoromethanesulfonic anhydride (0.082 mL, 0.488 mmol). After stirring for 2 h at room temperature, the reaction mixture was quenched with water and partitioned between 1.0M aqueous solution of Na₂CO₃ and DCM. The organic phase was dried over MgSO₄, filtered and concentrated in vacuo to yield residue which was purified by flash chromatography (silica gel, 0 to 5% MeOH in DCM) to yield (R)-4′-(6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl]-4-yl trifluoromethanesulfonate (81 mg, 35%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.78 (m, 2H), 0.88-0.99 (m, 2H), 1.39-1.58 (m, 2H), 1.63-1.93 (m, 5H), 1.95-2.06 (m, 1H), 2.31-2.67 (m, 1H), 3.02 (dd, J=12.0, 7.2 Hz, 0.5H), 3.21-3.40 (m, 1H), 3.47-3.86 (m, 4.5H), 7.40 (d, J=8.7 Hz, 2H), 7.64-7.76 (m, 6H); MS m/z 562.0 (M+H)⁺.

STEP C: (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one

To a solution of (R)-4′-(6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-[1,1′-biphenyl]-4-yl trifluoromethanesulfonate (75 mg, 0.134 mmol) in acetonitrile (2 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (33.5 mg, 0.161 mmol), aqueous 1.0M Na₂CO₃ (0.27 mL, 0.27 mmol) and bis(triphenylphosphine) palladium (II) chloride (4.91 mg, 0.007 mmol). The resulting mixture was bubbled with nitrogen for 5 min and heated to 85° C. for 2 h. The resulting mixture was diluted with DCM (30 mL), dried over MgSO₄, filtered and concentrated in vacuo to yield a residue which was purified by flash chromatography (silica gel, 0 to 5% MeOH in DCM) to yield a residue which was re-crystallized from MeCN to yield (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one (41 mg, 60%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.77 (m, 2H), 0.90-1.00 (m, 2H), 1.42-1.73 (m, 2H), 1.73-1.84 (m, 2H), 1.84-1.92 (m, 2H), 1.92-2.10 (m, 1H), 2.36-2.66 (m, 1H), 3.06 (dd, J=12.0, 7.1 Hz, 0.5H), 3.20-3.40 (m, 1H), 3.50-3.89 (m, 4.5H), 3.98 (s, 3H), 7.59 (m, J=8.2 Hz, 2H), 7.62-7.72 (m, 5H), 7.73-7.80 (m, 2H), 7.83 (s, 1H); MS m/z 494.0 (M+H)⁺.

Following the procedure described in Example 3, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data  21

5-(4″-Bromo-1,1′:4′,1″-terphenyl-4-yl)- 6-{[1-(cyclopropylcarbonyl)piperidin-4- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.66- 0.76 (m, 2 H), 0.87-0.96 (m, 2 H), 0.96-1.21 (m, 2 H), 1.49-1.56 (m, 1 H), 1.61-1.73 (m, 2 H), 1.73-1.83 (m, 2 H), 1.83-1.93 (m, 3 H), 2.48 (t, J = 12.2 Hz, 1 H), 2.99 (t, J = 11.8 Hz, 1 H), 3.69 (t, J = 8.2 Hz, 2 H), 4.16 (d, J = 11.8 Hz, 1 H), 4.53 (d, J = 10.9 Hz, 1 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.61 (d, J = 8.5 Hz, 2 H), 7.65-7.85 (m, 8 H); MS m/z 582 (M + H)⁺ m.p. 241.1° C.  23

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.71 (dd, J = 7.8, 3.1 Hz, 2 H), 0.89-0.97 (m, 2 H), 0.97-0.11 (m, 2 H), 1.47- 1.73 (m, 3 H), 1.73-1.83 (m, 2 H), 1.83-1.96 (m, 3 H), 2.49 (t, J = 12.3 Hz, 1 H), 2.99 (t, J = 12.8 Hz, 1 H), 3.69 (t, J = 8.1 Hz, 2 H), 4.03-4.32 (m, 1 H), 4.53 (d, J = 10.3 Hz, 1 H), 7.42 (dd, J = 7.6, 4.9 Hz, 1 H), 7.71 (t, J = 8.7 Hz, 4 H), 7.79 (dd, J = 8.3, 2.3 Hz, 4 H), 7.95 (d, J = 8.0 Hz, 1 H), 8.64 (d, J = 3.6 Hz, 1 H), 8.93 (br. s., 1 H); MS m/z 505 (M + H)⁺ m.p. 155.1° C.  56

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol- 4-yl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (dd, J = 7.8, 3.1 Hz, 2 H), 0.88-0.96 (m, 2 H), 0.97-1.33 (m, 3 H), 1.67 (td, J = 8.2, 4.3 Hz, 2 H), 1.73-1.81 (m, 2 H), 1.82-1.94 (m, 3 H), 2.33-2.63 (m, 1 H), 2.85-3.09 (m, 1 H), 3.60-3.75 (m, 2 H), 3.98 (s, 3 H), 4.06-4.27 (m, 1 H), 4.40-4.65 (m, 1 H), 7.55-7.62 (m, 2 H), 7.62-7.72 (m, 5 H), 7.72- 7.80 (m, 2 H), 7.83 (s, 1 H); MS m/z 508 (M + H)⁺ m.p. 186.8° C.  61

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-(4′-pyridin-4-ylbiphenyl-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 505 (M + H)⁺ m.p. 162.1° C.  62

6-{[1-(Cyclopropylcarbonyl)piperidin-4- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol- 5-yl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)⁺ m.p. 119.2° C. 122

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61-0.83 (m, 2 H), 0.84-1.06 (m, 2 H), 1.36-2.13 (m, 6 H), 2.28-2.71 (m, 1 H), 3.06 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.21-3.41 (m 1 H), 3.41-4.03 (m, 4.5 H), 7.43 (d, J = 4.7 Hz, 1 H), 7.60- 7.89 (m, 8 H), 7.95 (d, J = 7.7 Hz, 1 H), 8.64 (br. s., 1 H), 8.93 (br. s., 1 H); MS m/z 491 (M + H)⁺ m.p. 149.7° C.  59

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol- 4-yl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.84 (m, 2 H), 0.84-1.06 (m, 2 H), 1.23-1.38 (m, 1 H), 1.72-1.84 (m, 2 H), 1.84-1.99 (m, 2 H), 2.75-3.00 (m, 1 H), 3.61 (dd, J = 9.8, 5.6 Hz, 1 H), 3.90-4.15 (m, 4 H), 4.00 (s, 3 H), 4.23 (t, J = 8.2 Hz, 1 H), 7.54-7.72 (m, 6 H), 7.72-7.96 (m, 4 H); MS m/z 480 (M + H)⁺ m.p. 203.4° C.  60

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4′-pyridin-3-ylbiphenyl-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.65- 0.77 (m, 2 H), 0.91 (t, J = 3.9 Hz, 2 H), 1.25-1.36 (m, 1 H), 1.75-1.84 (m, 2 H), 1.84-1.94 (m, 2 H), 2.77-2.96 (m, 1 H), 3.61 (dd, J = 9.9, 5.8 Hz, 1 H), 3.89-4.16 (m, 4 H), 4.25 (t, J = 8.3 Hz, 1 H), 7.42 (dd, J = 7.9, 4.9 Hz, 1 H), 7.66-7.89 (m, 8 H), 7.95 (dt, J = 7.9, 1.9 Hz, 1 H), 8.64 (dd, J = 4.8, 1.5 Hz, 1 H), 8.93 (d, J = 2.2 Hz, 1 H); MS m/z 477 (M + H)⁺

Example 4 2-[4-(1,3-Benzoxazol-2-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one (Compound #36)

To a flask under argon was added (R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (122 mg, 0.275 mmol), benzo[d]oxazole (40 mg, 0.329 mmol), K₂CO₃ (76 mg, 0.549 mmol), Pd(OAc)₂ (1.3 mg, 0.0055 mmol), Cu(OAc)₂ (10.7 mg, 0.0549 mmol), PPh₃ (36 mg, 0.137 mmol) and 1 mL of toluene. The reaction mixture was heated at 110° C. for 6 hrs, the solvent evaporated, and the residue purified by preparative reverse-phase chromatography to yield 2-[4-(1,3-benzoxazol-2-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one (65.3 mg, 47%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.79 (d, J=5.1 Hz, 2H), 0.92-1.07 (m, 2H), 1.40-1.76 (m, 2H), 1.83-2.31 (m, 9H), 2.33-2.58 (m, 1H), 3.03-3.32 (m, 1H), 3.32-3.91 (m, 5H), 7.39-7.49 (m, 2H), 7.65 (d, J=6.6 Hz, 1H), 7.86 (t, J=7.3 Hz, 3H), 8.49 (d, J=6.6 Hz, 2H). MS m/z 483.3 (M+H)⁺.

Example 5 (R)-Methyl 2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (Compound #14)

STEP A: 4-tert-Butyl 4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate

A mixture tert-butyl 4-amino-4-carbamoylpiperidine-1-carboxylate (0.848 g, 3.41 mmol), 4-bromobenzoic acid (0.687 g, 3.41 mmol), EDCI (0.655 g, 3.41 mmol), HOBt (0.462 g, 3.41 mmol) and DIPEA (0.59 mL, 3.41 mmol) in DMF (16 mL) was stirred at room temperature for 1 day. The reaction mixture was partitioned between EtOAc and aqueous saturated NaHCO₃. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 4-tert-butyl 4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate (1.21 g, 83%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.40 (s, 9H), 1.76-1.93 (m, 2H), 2.01-2.19 (m, 2H), 3.09 (br. s., 2H), 3.57-3.80 (m, 2H), 6.93 (br. s., 1H), 7.16 (br. s., 1H), 7.68 (d, J=8.6 Hz, 2H), 7.84 (d, J=8.6 Hz, 2H), 8.21 (s, 1H); MS m/z 450.1 (M+Na)⁺).

STEP B: tert-Butyl 2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

A mixture of 4-tert-butyl 4-(4-bromobenzamido)-4-carbamoylpiperidine-1-carboxylate (1.6 g, 3.75 mmol) and NaOH (0.75 g, 18.76 mmol) in H₂O (3.80 mL) and MeOH (65 mL) was stirred at 65° C. for 1 day. The reaction mixture was partitioned between water (400 mL) and EtOAc (2×350 mL). The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (1.53 g, 100%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.35-1.53 (m, 11H), 1.61-1.74 (m, 2H), 3.28 (br. s., 3H), 3.80-3.98 (m, 2H), 7.77 (d, J=8.3 Hz, 2H), 7.94 (d, J=8.1 Hz, 2H); MS m/z 410.0 (M+H)⁺.

STEP C: 2-(4-Bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (tert-butyl 2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (400 mg, 0.98 mmol) in 1,4-dioxane (7 mL) was added 4M HCl in 1,4-dioxane (8 mL). After stirring at room temperature for 5 h, the reaction mixture was concentrated to yield 2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one as its corresponding HCl salt, as a solid; which was directly used in the next step.

MS m/z 310.0 (M+H)⁺.

STEP D: Methyl 2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of 2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one HCl salt (172 mg, 0.5 mmol) in DCM (15 mL) and DIPEA (0.43 mL, 2.5 mmol) was added methyl chloroformate (49.6 mg, 0.52 mmol) at 0° C. After stirring at room temperature overnight, the reaction mixture was partitioned between aqueous NaHCO₃ and DCM. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield methyl 2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (183 mg, 100%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.52-1.64 (m, 2H), 1.89-2.07 (m, 2H), 3.45-3.59 (m, 2H), 3.76 (s, 3H), 3.98-4.25 (m, 2H), 7.64-7.71 (m, 2H), 7.77-7.84 (m, 2H); MS m/z 368.0 (M+H)⁺.

STEP E: (S)-Methyl 2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of methyl 2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (100 mg, 0.27 mmol) and (R)-tert-butyl 3-(bromomethyl)pyrrolidine-1-carboxylate (144 mg, 0.54 mmol) in DMF (4.5 mL) was added Cs₂CO₃ (222 mg, 0.68 mmol). After stirring at room temperature for 5 min and 65° C. for 17 h, the reaction mixture was partitioned between aqueous NaHCO₃ and EtOAc. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 40% EtOAc/heptane) to yield (S)-methyl 2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (122 mg, 81%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.17 (br. s., 1H), 1.41 (s, 9H), 1.46-1.56 (m, 2H), 1.67-1.82 (m, 2H), 1.87-2.02 (m, 2H), 2.23 (d, J=6.8 Hz, 1H), 2.71-2.87 (m, 1H), 3.09-3.39 (m, 2H), 3.47 (s, 3H), 3.53-3.68 (m, 2H), 3.72 (s, 3H), 3.94-4.20 (m, 2H), 7.45 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.1 Hz, 2H); MS m/z 540.0 (M+H)⁺.

STEP F: (R)-Methyl 2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of (S)-methyl 2-(4-bromophenyl)-3-((1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (162 mg, 0.295 mmol) in 1,4-dioxane (3 mL) was added 4M HCl in 1,4-dioxane (5 mL). After stirring overnight at room temperature the reaction mixture was concentrated to yield (R)-methyl 2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate as its corresponding HCl salt, as a solid; which was directly used into the next step. MS m/z 451.0 (M+H)⁺.

STEP G: (R)-Methyl 2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate

To a stirring solution of (R)-methyl 2-(4-bromophenyl)-4-oxo-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (150 mg, 0.334 mmol) in DCM (10 mL) and DIPEA (0.28 mL, 1.67 mmol) was added cyclopropanecarbonyl chloride (0.038 mL, 0.40 mmol). After stirring at room temperature for 3 h, the reaction mixture was partitioned between aqueous NaHCO₃ and DCM. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield (R)-methyl 2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (130 mg, 75%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.68-0.80 (m, 2H), 0.90-0.99 (m, 2H), 1.38-1.64 (m, 5H), 1.72-1.84 (m, 1H), 1.87-2.04 (m, 3H), 2.18-2.44 (m, 1H), 2.95 (dd, J=12.0, 7.1 Hz, 1H), 3.13-3.34 (m, 1H), 3.41-3.71 (m, 7H), 3.73 (s, 3H), 3.96-4.23 (m, 2H), 7.46 (dd, J=8.3, 5.9 Hz, 2H), 7.62-7.73 (m, 2H); MS m/z 517.0 (M+H)⁺.

STEP H: (R)-Methyl 2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (Compound #14)

To a solution of (R)-methyl 2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (50 mg, 0.097 mmol) and benzofuran-5-ylboronic acid (24.0 mg, 0.145 mol) in DME (2 mL) was added under argon aqueous 2M Na₂CO₃ (0.1 mL, 0.20 mmol) and Pd(PPh₃)₄ (3.4 mg, 0.003 mmol). The reaction mixture was refluxed for 16 h, filtered, concentrated in vacuo and the resulting residue was purified by flash chromatography (silica gel, 2.5% MeOH/DCM) to yield (R)-methyl 2-(4-(benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8-carboxylate (45 mg, 84%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.71 (dd, J=7.6, 2.9 Hz, 2H), 0.89-0.96 (m, 2H), 1.38-1.68 (m, 4H), 1.82 (dd, J=11.5, 5.1 Hz, 1H), 1.89-2.09 (m, 3H), 2.38-2.54 (m, 1H), 3.00 (dd, J=12.0, 7.1 Hz, 1H), 3.15-3.35 (m, 1H), 3.42-3.70 (m, 5H), 3.71-3.78 (m, 4H), 4.15 (br. s., 2H), 6.85 (d, J=2.0 Hz, 1H), 7.53-7.58 (m, 1H), 7.61 (d, J=8.6 Hz, 1H), 7.63-7.72 (m, 3H), 7.73-7.81 (m, 2H), 7.84 (s, 1H); MS m/z 555.0 (M+H)⁺.

Following the procedure described in Example 5, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 15

Methyl 3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-4- oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8- carboxylate ¹H NMR (400 MHz, CDCl₃) δ ppm 0.64- 0.77 (m, 2 H), 0.88-0.99 (m, 2 H), 1.42- 1.64 (m, 4 H), 1.77-2.09 (m, 3 H), 2.23- 2.53 (m, 1 H), 2.94-3.34 (m, 1 H), 3.46- 3.72 (m, 5 H), 3.72-3.79 (m, 4 H), 3.96- 4.26 (m, 2 H), 6.62 (br. s., 1 H), 7.28 (br. s., 1 H), 7.43-7.49 (m, 2 H), 7.63 (t, J = 7.8 Hz, 2 H), 7.74-7.83 (m, 2 H), 7.90 (s, 1 H), 8.62 (br. s., 1 H); MS m/z 554.2 (M + H)⁺ 16

Methyl 2-[4-(1-benzofuran-5-yl)phenyl]-3- {[1-(cyclopropylcarbonyl)azetidin-3- yl]methyl}-4-oxo-1,3,8-triazaspiro[4.5]dec- 1-ene-8-carboxylate ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70 (dd, J = 7.8, 3.4 Hz, 2 H), 0.85-0.94 (m, 2 H), 1.22-1.33 (m, 1 H), 1.54 (d, J = 13.2 Hz, 2 H), 1.92-2.06 (m, 2 H), 2.75 (br. s., 1 H), 3.44-3.61 (m, 3 H), 3.75 (s, 3 H), 3.84- 4.08 (m, 5 H), 4.08-4.24 (m, 2 H), 6.86 (d, J = 2.0 Hz, 1 H), 7.56 (dd, J = 8.6, 1.7 Hz, 1 H), 7.62 (d, J = 8.6 Hz, 1 H), 7.65 (d, J = 8.3 Hz, 2 H), 7.70 (d, J = 2.0 Hz, 1 H), 7.78 (d, J = 8.3 Hz, 2 H), 7.84 (d, J = 1.5 Hz, 1 H); MS m/z 541.0 (M + H)⁺ 17

Methyl 3-{[1-(cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-4- oxo-1,3,8-triazaspiro[4.5]dec-1-ene-8- carboxylate ¹H NMR (400 MHz, CDCl₃) δ ppm 0.70 (dd, J = 7.8, 3.2 Hz, 2 H), 0.91 (br. s., 2 H), 1.21- 1.34 (m, 1 H), 1.54 (d, J = 12.7 Hz, 2 H), 1.90-2.06 (m, 2 H), 2.75 (br. s., 1 H), 3.45- 3.63 (m, 3 H), 3.75 (s, 3 H), 3.82-4.07 (m, 4 H), 4.07-4.25 (m, 2 H), 6.64 (br. s., 1 H), 7.29 (t, J = 2.7 Hz, 1 H), 7.42-7.51 (m, 2 H), 7.62 (m, J = 8.3 Hz, 2 H), 7.80 (m, J = 8.1 Hz, 2 H), 7.91 (s, 1 H), 8.56 (br. s., 1 H); MS m/z 540.3 (M + H)⁺

Example 6 R)-2-(4-(1H-Indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #63

and (R)-2-(4-(1H-indol-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #81)

STEP A: 4-Amino-1-benzylpiperidine-4-carbonitrile

To a solution of ammonium chloride (17.3 g, 323 mmol) in water (200 mL) was added successively aqueous 25% ammonia (25 mL, 332 mmol) and 1-benzylpiperidin-4-one (11.43 g, 60 mmol). The resulting mixture was stirred at room temperature for 20 min and sodium cyanide (14.7 g, 300 mmol) was added in portions over 15 min. After stirring for 1 day, the reaction mixture was partitioned between water (200 mL) and DCM (2×200 mL). The organic phase was dried over MgSO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 50% EtOAc/heptanes to 100% EtOAc) to yield 4-amino-1-benzylpiperidine-4-carbonitrile (6.15 g, 47%).

¹H NMR (300 MHz, CDCl₃) δ ppm 1.69-1.86 (m, 4H), 2.00 (dt, J=13.1, 2.1 Hz, 2H), 2.27-2.45 (m, 2H), 2.83 (dt, J=12.4, 3.6 Hz, 2H), 3.55 (s, 2H), 7.21-7.39 (m, 5H); MS m/z 216 (M+H)⁺.

STEP B: 4-Amino-1-benzylpiperidine-4-carboxamide

To a solution of 4-amino-1-benzylpiperidine-4-carbonitrile (6.15 g, 28.6 mmol) in DCM (70 mL) at −5° C. was added 95-97% sulfuric acid (50 mL). The reaction mixture was stirred at 0 to 5° C. overnight and the organic layer was discarded. The resulting mixture was poured onto crushed ice (1000 mL) and the pH adjusted to pH 9 with aqueous 5N NaOH, keeping the temperature below 10° C. The resulting mixture was partitioned between water and EtOAc (3×500 mL). The organic phase was dried over MgSO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 5% MeOH in DCM) to yield 2-(4-bromophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (5.06 g, 76%).

¹H NMR (300 MHz, CDCl₃) δ ppm 1.29-1.57 (m, 4H), 2.14-2.39 (m, 4H), 2.71-2.84 (m, 2H), 3.55 (s, 2H), 5.41 (br. s., 1H), 7.20-7.38 (m, 5H), 7.45 (br. s., 1H); MS m/z 234 (M+H)⁺.

STEP C: 1-Benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide

A mixture 4-amino-1-benzylpiperidine-4-carboxamide (2 g, 8.31 mmol), 4-bromobenzoic acid (1.67 g, 8.31 mmol), EDCI (1.59 g, 8.31 mmol), HOBt (1.12 g, 8.31 mmol) and DIPEA (1.43 mL, 8.31 mmol) in DMF (45 mL) was stirred at room temperature for 1 day. The reaction mixture was partitioned between EtOAc and aqueous saturated NaHCO₃. The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 1-benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide (3.4 g, 99%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.74-1.87 (m, 2H), 1.97-2.14 (m, 4H), 2.45 (d, J=11.5 Hz, 2H), 3.21 (s, 2H), 3.29 (s, 2H), 6.73 (s, 1H), 6.94 (s, 1H), 7.04-7.23 (m, 5H), 7.54 (d, J=8.3 Hz, 2H), 7.67 (d, J=8.6 Hz, 2H), 7.91 (s, 1H); MS m/z 418.0 (M+H)⁺.

STEP D: 8-Benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

A mixture of 1-benzyl-4-(4-bromobenzamido)piperidine-4-carboxamide (2 g, 4.8 mmol) and NaOH (0.96 g, 24.0 mmol) in H₂O (4.81 mL) and MeOH (80 mL) was stirred at 65° C. for 1 day. The reaction mixture was partitioned between water (300 mL) and EtOAc (2×300 mL). The organic phase was washed with brine, dried over Na₂SO₄, filtered and concentrated in vacuo to yield 8-benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (1.56 g, 82%).

¹H NMR (400 MHz, DMSO-d₆) δ ppm 1.36-1.54 (m, 2H), 1.76-1.90 (m, 2H), 2.42-2.45 (m, 2H), 2.70-2.82 (m, 2H), 3.56 (s, 2H), 7.21-7.28 (m, 1H), 7.30-7.37 (m, 4H), 7.75 (d, J=7.8 Hz, 2H), 7.90 (br. s., 2H); MS m/z 400.0 (M+H)⁺.

STEP E: (5)-tert-Butyl 3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate

To a stirring solution of 8-benzyl-2-(4-bromophenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.95 g, 2.38 mmol) and (R)-tert-butyl 3-(iodomethyl)pyrrolidine-1-carboxylate (1.33 g, 4.77 mmol) in DMF (10 mL) was added K₂CO₃ (0.66 g, 4.77 mmol). After stirring at 65° C. for 48 h, the reaction mixture was partitioned between water and EtOAc. The organic phase was washed with brine, dried over MgSO₄, filtered and concentrated in vacuo to yield a residue. The residue was purified by flash chromatography (silica gel, 2-5% MeOH/DCM) to yield (S)-tert-butyl 3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (0.75 g, 57%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.17 (br. s., 1H), 1.41 (s, 9H), 1.46-1.56 (m, 2H), 1.67-1.82 (m, 2H), 1.87-2.02 (m, 2H), 2.23 (d, J=6.8 Hz, 1H), 2.71-2.87 (m, 1H), 3.09-3.39 (m, 2H), 3.47 (s, 3H), 3.53-3.68 (m, 2H), 3.72 (s, 3H), 3.94-4.20 (m, 2H), 7.45 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.1 Hz, 2H); MS m/z 540.0 (M+H)⁺.

STEP F: (R)-8-Benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (5)-tert-butyl 3-((8-benzyl-2-(4-bromophenyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (5.05 g, 8.68 mmol) in 1,4-dioxane (20 mL) was added 4M HCl in 1,4-dioxane (20 mL). After stirring for 4 h at room temperature the reaction mixture was diluted with diethyl ether; the precipitate was filtered off, washed with diethyl ether and dried to yield (R)-8-benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one, as its corresponding bis-HCl salt (5.06 g, 95%).

MS m/z 481.0 (M+H)⁺.

STEP G: (R)-8-Benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (R)-8-benzyl-2-(4-bromophenyl)-3-(pyrrolidin-3-ylmethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (5.05 g, 8.66 mmol) in DCM (100 mL) and triethylamine (6.04 mL, 43.3 mmol) was added at 0° C. cyclopropanecarbonyl chloride (0.87 mL, 9.53 mmol). After stirring at room temperature for 1 h, MeOH (5 mL) was added to the solution and the reaction mixture was partitioned between aqueous 1M NaOH and DCM. The organic phase was dried over MgSO₄, filtered and concentrated in vacuo to yield ((R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (4.94 g, 99%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.68-0.80 (m, 2H), 0.90-0.99 (m, 2H), 1.38-1.64 (m, 5H), 1.72-1.84 (m, 1H), 1.87-2.04 (m, 3H), 2.18-2.44 (m, 1H), 2.95 (dd, J=12.0, 7.1 Hz, 1H), 3.13-3.34 (m, 1H), 3.41-3.71 (m, 7H), 3.73 (s, 3H), 3.96-4.23 (m, 2H), 7.46 (dd, J=8.3, 5.9 Hz, 2H), 7.62-7.73 (m, 2H); MS m/z 549.0 (M+H)⁺.

STEP H: (R)-2-(4-(1H-Indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl) Pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #63)

((R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.382 g, 0.695 mmol), 1H-indol-5-yl-5-boronic acid (0.134 g, 0.834 mmol), tetrakis(triphenylphosphine) palladium (0.040 g, 0.035 mmol), potassium carbonate (0.192 g, 0.241 mmol), dioxane (25 mL) and water (2 mL) were combined and the resulting mixture was heated at reflux for 16 h. The mixture was diluted with water and extracted with ethyl acetate. The extracts were concentrated to a dark oil, which was purified by flash chromatography (silica gel, 0 to 5% methanol in dichloromethane) to yield (R)-2-(4-(1H-indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one as a slightly pink solid (0.183 g) ¹H NMR (400 MHz, CDCl₃) δ ppm 0.67-0.73 (m, 2H), 0.89-0.97 (m, 2H), 1.39-1.66 (m, 3H), 1.75-2.02 (m, 2H), 2.08-2.21 (m, 2H), 2.28-2.51 (m, 1H), 2.68 (t, J=11.1 Hz, 2H), 2.83-2.95 (m, 1H), 3.02 (dd, J=12.1, 7.1 Hz, 1H), 3.13-3.34 (m, 1H), 3.43-3.76 (m, 7H), 6.61 (br. s., 1H), 7.22-7.29 (m, 2H), 7.30-7.39 (m, 4H), 7.44 (d, J=8.6 Hz, 2H), 7.61 (t, J=8.1 Hz, 2H), 7.77 (dd, J=10.1, 8.1 Hz, 2H), 7.89 (s, 1H), 8.73 (d, J=7.1 Hz, 1H) MS m/z 586.3 (M+H)⁺.

STEP I: (R)-2-(4-(1H-Indo)-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #81)

(R)-2-(4-(1H-indol-5-yl)phenyl)-8-benzyl-3-((1-(cyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.050 g, 0.085 mmol) was dissolved in a mixture of formic acid (0.5 mL) in methanol (5 mL). 10% palladium on carbon (0.005 g) was added. The resulting mixture was heated at reflux for 16 h. The mixture was then diluted with brine and extracted 3 times with ethyl acetate. The combined ethyl acetate extracts were washed with saturated aqueous sodium bicarbonate, filtered through diatomaceous earth, and concentrated under vacuum. The resulting oil was purified by flash chromatography (silica gel, 0 to 5% methanol in dichloromethane) to yield (R)-2-(4-(1H-Indo)-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one as a white solid (0.003 g).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.60-0.78 (m, 2H), 0.84-0.97 (m, 2H), 1.15-1.33 (m, 1H), 1.37-1.56 (m, 2H), 1.75-1.99 (m, 1H), 2.05-2.21 (m, 2H), 2.27-2.52 (m, 4H), 2.64 (t, J=10.8 Hz, 2H), 2.74-2.90 (m, 2H), 3.02 (dd, J=12.0, 6.8 Hz, 1H), 3.13-3.33 (m, 1H), 3.61 (m, J=13.4 Hz, 5H), 6.64 (t, J=2.2 Hz, 0H), 7.19-7.34 (m, 1H), 7.41-7.55 (m, 2H), 7.60-7.66 (m, 2H), 7.79 (dd, J=8.3, 6.4 Hz, 2H), 7.90 (s, 1H), 8.34 (br. s., 1H) MS m/z 510.0 (M+H)⁺.

Following the procedure described in Example 6, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compound of formula (I) of the invention was prepared.

ID No. Structure Name and data 193

8-Benzyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-isoquinolin-6-ylphenyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63- 0.76 (m, 2 H), 0.84-1.01 (m, 2 H), 1.36- 1.71 (m, 3 H), 1.71-2.00 (m, 2 H), 2.07- 2.26 (m, 2 H), 2.26-2.56 (m, 1 H), 2.68 (t, J = 10.7 Hz, 2 H), 2.78-3.06 (m, 3 H), 3.12-3.40 (m, 1 H), 3.41-3.84 (m, 6 H), 7.20-7.43 (m, 5 H), 7.67-7.77 (m, 3 H), 7.80-7.95 (m, 3 H), 8.01-8.16 (m, 2 H), 8.60 (d, J = 5.8 Hz, 1 H), 9.32 (s, 1 H); MS m/z 554.2 (M + H)⁺

Example 7 R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #128

and (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #139)

STEP A: (R)-2-(4-Bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring suspension of (R)-8-benzyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (4.94 g, 8.54 mmol) and potassium bicarbonate (10.26 g, 102.5 mmol) in DCM (100 mL) was added 1-chloroethyl chloroformate (2.65 mL, 24.6 mmol). After refluxing for 1.5 h the reaction mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in MeOH (100 mL) and the solution was refluxed for 1 h, cooled down to room temperature and concentrated in vacuo. The residue was triturated with diethyl ether and the solid was filtered and dried to yield (R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (4.5 g, 99%).

MS m/z 459.0 (M+H)⁺.

STEP B: (R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #128)

(R)-2-(4-Bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (1 g, 1.9 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (0.652 g, 2.28 mmol), aqueous 1.0M Na₂CO₃ (4 mL, 4 mmol) and acetonitrile (20 mL) were combined and bubbled with nitrogen for 15 min. Bis(triphenylphosphine)palladium (II) chloride (0.067 g, 0.095 mmol) was added and the mixture was heated at 85° C. for 1.5 h. The resulting mixture was diluted with water and extracted with DCM. The extracts were concentrated to yield a residue which was purified by flash chromatography (silica gel, DCM/MeOH/NH₄OH 9/0.9/0.1) to yield (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.573 g, 54%).

¹H NMR (300 MHz, DMSO-d6) 6 ppm 0.56-0.71 (m, 4H), 1.26-2.04 (m, 7H), 2.05-2.39 (m, 1H), 2.74-3.60 (m, 9H), 3.65 (t, J=6.9 Hz, 2H), 4.09 (s, 3H), 7.71-7.85 (m, 4H), 7.86-7.95 (m, 2H), 8.08-8.19 (m, 2H); MS m/z 511.0 (M+H)⁺.

STEP C: (R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #139)

To a stirring solution of (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (80 mg, 0.147 mmol) in DCM (5 mL) and Et₃N (0.20 mL, 1.43 mmol) was added isobutyryl chloride (0.019 mL, 0.176 mmol). After stirring at room temperature for 1 h, the reaction mixture was quenched with MeOH (0.5 mL) and partitioned between aqueous 1.0 M NaOH and DCM. The organic phase was dried over MgSO₄, filtered and concentrated in vacuo to yield a residue which was purified by flash chromatography (silica gel, 0 to 7.5% MeOH in DCM) and re-purified by reverse phase prep-HPLC to yield (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-isobutyryl-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (74 mg, 86%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (d, J=4.7 Hz, 2H), 0.79-1.05 (m, 2H), 1.14-1.25 (m, 6H), 1.27-2.14 (m, 8H), 2.14-2.61 (m, 1H), 2.71-3.10 (m, 2H), 3.10-3.84 (m, 6H), 3.86-4.08 (m, 1H), 4.06-4.21 (m, 3H), 4.52 (br. s., 1H), 7.51 (d, J=8.8 Hz, 1H), 7.61-7.75 (m, 3H), 7.75-7.85 (m, 2H), 7.97 (s, 1H), 8.07 (s, 1H); MS m/z 581.0 (M+H)⁺; m.p. 104.2° C.

Following the procedure described in Example 7, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 106

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.2 Hz, 4 H), 1.25-2.00 (m, 7 H), 2.01-2.40 (m, 1 H), 2.76- 3.76 (m, 11 H), 7.87 (dd, J = 8.1, 4.9 Hz, 2 H), 7.93 (d, J = 5.8 Hz, 1 H), 7.97-8.17 (m, 3 H), 8.26 (d, J = 8.7 Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J = 5.8 Hz, 1 H), 9.37 (s, 1 H); MS m/z 508 (M + H)⁺ 130

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one MS m/z 483 (M + H)⁺ 131

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-[4-(1-methyl-1H- indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 497 (M + H)⁺ 132

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one MS m/z 494 (M + H)⁺ 133

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.53-0.72 (m, 4 H), 1.25-1.93 (m, 5 H), 2.08-2.40 (m, 1 H), 2.74-3.59 (m, 10 H), 3.65 (t, J = 6.9 Hz, 2 H), 4.08 (br. s., 1 H), 6.98-7.08 (m, 1 H), 7.62-7.83 (m, 4 H), 7.83-7.93 (m, 2 H), 7.99-8.09 (m, 2 H); MS m/z 497 (M + H)⁺ 155

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.53-0.70 (m, 4 H), 1.22-1.95 (m, 6 H), 2.03-2.39 (m, 1 H), 2.48 (s, 3 H), 2.76-3.27 (m, 7 H), 3.36-3.59 (m, 3 H), 3.58-3.72 (m, 2 H), 6.66 (s, 1 H), 7.60 (s, 2 H), 7.70-7.82 (m, 2 H), 7.82-7.92 (m, 3 H); MS m/z 511 (M + H)⁺ m.p. 95.5° C. 138

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol- 5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (dd, J = 7.5, 3.2 Hz, 2 H), 0.94 (br. s., 2 H), 1.32-1.68 (m, 4 H), 1.74-2.12 (m, 3 H), 2.16 (s, 3 H), 2.34-2.58 (m, 1 H), 2.80-3.99 (m, 9 H), 4.13 (s, 3 H), 4.37-4.59 (m, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.67 (dd, J = 8.0, 4.8 Hz, 3 H), 7.80 (dd, J = 8.2, 3.9 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s, 1 H); MS m/z 553 (M + H)⁺ m.p. 111.2° C. 140

8-(Cyclopropylcarbonyl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol- 5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.76 (m, 2 H), 0.76-0.88 (m, 2 H), 0.88-0.99 (m, 2 H), 1.04 (br. s., 2 H), 1.36-1.56 (m, 2 H), 1.71-2.63 (m, 6 H), 2.85-3.95 (m, 9 H), 4.14 (s, 3 H), 4.17-4.33 (m, 1 H), 4.37- 4.59 (m, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.69 (d, J = 8.8 Hz, 3 H), 7.75- 7.86 (m, 2 H), 7.98 (s, 1 H), 8.07 (s, 1 H); MS m/z 579 (M + H)⁺ m.p. 114.8° C. 141

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2- [4-(1-methyl-1H-indazol-5-yl)phenyl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.71 (d, J = 4.4 Hz, 2 H), 0.93 (br. s., 2 H), 1.35-1.76 (m, 4 H), 1.74-2.13 (m, 4 H), 2.31 (s, 6 H), 2.35-2.59 (m, 1 H), 2.85-3.86 (m, 9 H), 4.04- 4.18 (m, 1 H), 4.13 (s, 3 H), 4.31- 4.55 (m, 1 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.61-7.74 (m, 3 H), 7.74-7.86 (m, 2 H), 7.97 (s, 1 H), 8.06 (s, 1 H); MS m/z 596 (M + H)⁺ m.p. 127.5° C. 142

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2- (4-isoquinolin-6-ylphenyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.72 (dt, J = 4.9, 2.4 Hz, 2 H), 0.84- 1.03 (m, 2 H), 1.33-2.14 (m, 9 H), 2.33 (s, 6 H), 2.36-2.63 (m, 1 H), 2.85-3.99 (m, 8 H), 4.03-4.32 (m, 1 H), 4.30-4.60 (m, 1 H), 7.64-7.83 (m, 3 H), 7.89 (dd, J = 8.7, 2.1 Hz, 3 H), 7.99-8.19 (m, 2 H), 8.60 (d, J = 5.6 Hz, 1 H), 9.32 (s, 1 H); MS m/z 593 (M + H)⁺ m.p. 94.2° C. 143

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-8-(2-methylpropanoyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61-0.80 (m, 2 H), 0.83-1.02 (m, 2 H), 1.13-1.27 (m, 6 H), 1.35-1.71 (m, 4 H), 1.86-2.14 (m, 3 H), 2.18- 2.62 (m, 1 H), 2.87 (dt, J = 13.5, 6.7 Hz, 1 H), 2.92-3.89 (m, 9 H), 3.98 (d, J = 12.0 Hz, 1 H), 4.50 (d, J = 12.4 Hz, 1 H), 7.75 (d, J = 7.8 Hz, 3 H), 7.89 (dd, J = 8.6, 2.0 Hz, 2 H), 7.97- 8.20 (m, 2 H), 8.61 (br. s., 1 H), 9.34 (br. s., 1 H); MS m/z 578 (M + H)⁺ m.p. 129.9° C. 144

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.65-0.80 (m, 2 H), 0.83-1.02 (m, 2 H), 1.36-1.69 (m, 4 H), 1.88-2.13 (m, 3 H), 2.17 (s, 3 H), 2.20-2.61 (m, 1 H), 2.79-4.01 (m, 9 H), 4.38- 4.56 (m, 1 H), 7.68-7.82 (m, 3 H), 7.84-7.96 (m, 3 H), 8.01-8.16 (m, 2 H), 8.60 (d, J = 5.5 Hz, 1 H), 9.33 (br. s., 1 H); MS m/z 550 (M + H)⁺ m.p. 123.1° C. 134

2-[4-(1-Benzofuran-5-yl)phenyl]-8- (cyclopropylcarbonyl)-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.70 (m, 4 H), 1.25-1.93 (m, 7 H), 2.08-2.39 (m, 1 H), 2.75-3.03 (m, 4 H), 3.03-3.59 (m, 6 H), 3.65 (t, J = 6.9 Hz, 2 H), 4.08 (br. s., 1 H), 7.04 (d, J = 1.6 Hz, 1 H), 7.61-7.83 (m, 4 H), 7.82-7.93 (m, 2 H), 8.00-8.11 (m, 2 H); MS m/z 551 (M + H)⁺ m.p. 93.6° C. 149

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(N,N-dimethylglycyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.56-0.68 (m, 4 H), 1.14-1.30 (m, 3 H), 1.30-1.43 (m, 1 H), 1.44-1.60 (m, 2 H), 1.62-1.79 (m, 1 H), 1.79- 1.99 (m, 1 H), 2.35 (s, 6 H), 2.55- 2.71 (m, 1 H), 3.13-3.27 (m, 2 H), 3.67-3.81 (m, 2 H), 3.88 (d, J = 7.3 Hz, 2 H), 3.96 (d, J = 13.3 Hz, 1 H), 4.13 (t, J = 8.2 Hz, 1 H), 4.28 (d, J = 12.9 Hz, 1 H), 7.04 (d, J = 1.9 Hz, 1 H), 7.65-7.76 (m, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.90 (m, J = 8.2 Hz, 2 H), 7.96-8.12 (m, 2 H); MS m/z 568 (M + H)⁺ m.p. 130.1° C. 150

8-Acetyl-2-[4-(1-benzofuran-5- yl)phenyl]-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.6 Hz, 4 H), 1.41-1.95 (m, 6 H), 2.07 (s, 3 H), 2.1-2.3 (m, 1 H), 2.77-2.92 (m, 0.5 H), 2.96-3.30 (m, 3.5 H), 3.36-3.60 (m, 3 H), 3.66 (t, J = 7.1 Hz, 2 H), 3.86 (d, J = 13.7 Hz, 1 H), 4.29 (d, J = 12.9 Hz, 1 H), 7.04 (d, J = 1.8 Hz, 1 H), 7.65-7.76 (m, 2 H), 7.76-7.85 (m, 2 H), 7.85-7.92 (m, 2 H), 7.97-8.10 (m, 2 H); MS m/z 539 (M + H)⁺ m.p. 96.6° C. 151

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-methylpropanoyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.63 (d, J = 5.5 Hz, 4 H), 0.94-1.11 (m, 6 H), 1.42-1.94 (m, 6 H), 2.10- 2.41 (m, 1 H), 2.74-3.29 (m, 5 H), 3.37-3.62 (m, 3 H), 3.61-3.72 (m, 2 H), 3.98 (d, J = 13.5 Hz, 1 H), 4.32 (d, J = 11.7 Hz, 1 H), 7.04 (d, J = 1.8 Hz, 1 H), 7.63-7.76 (m, 2 H), 7.76-7.85 (m, 2 H), 7.85-7.95 (m, 2 H), 7.99- 8.11 (m, 2 H); MS m/z 567 (M + H)⁺ m.p. 105.5° C. 152

2-[4-(1-Benzofuran-5-yl)phenyl]-8- (cyclopropylcarbonyl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.51-0.68 (m, 4 H), 0.68-0.89 (m, 4 H), 1.38-1.94 (m, 7 H), 1.95-2.11 (m, 1 H), 2.11-2.40 (m, 1 H), 2.77- 2.95 (m, 0.5 H), 3.11 (m, 2.5 H), 3.39- 3.77 (m, 5 H), 4.15-4.39 (m, 2 H), 7.04 (s, 1 H), 7.65-7.77 (m, 2 H), 7.77-7.85 (m, 2 H), 7.85-7.98 (m, 2 H), 7.98-8.14 (m, 2 H); MS m/z 565 (M + H)⁺ m.p. 115.1° C. 153

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.55-0.72 (m, 4 H), 1.42-1.97 (m, 6 H), 2.22 (s, 6 H), 2.24-2.41 (m, 1 H), 2.86 (dd, J = 12.0, 7.4 Hz, 0.5 H), 2.97- 3.29 (m, 5.5 H), 3.37-3.62 (m, 3 H), 3.62-3.73 (m, 2 H), 4.07 (d, J = 13.1 Hz, 1 H), 4.29 (d, J = 12.8 Hz, 1 H), 7.05 (d, J = 1.6 Hz, 1 H), 7.66- 7.77 (m, 2 H), 7.77-7.85 (m, 2 H), 7.85-7.96 (m, 2 H), 8.00-8.12 (m, 2 H); MS m/z 582 (M + H)⁺ m.p. 92° C. 135

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-[4-(1-methyl-1H- indazol-5-yl)phenyl]-8-(2- methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 567 (M + H)⁺ m.p. 160.8° C. 136

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-8-(N,N-dimethylglycyl)-2- [4-(1-methyl-1H-indazol-5-yl)phenyl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 582 (M + H)⁺ m.p. 102.3° C. 137

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-2-(4-isoquinolin-6- ylphenyl)-8-(2-methylpropanoyl)- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.50-0.72 (m, 4 H), 0.91-1.16 (m, 6 H), 1.31-1.44 (m, 1 H), 1.44-1.91 (m, 4 H), 2.54-2.71 (m, 1 H), 2.85- 3.02 (m, 1 H), 3.08-3.27 (m, 1 H), 3.34-3.42 (m, 1 H), 3.46-3.66 (m, 1 H), 3.66-3.81 (m, 2 H), 3.88 (d, J = 7.4 Hz, 2 H), 3.98 (d, J = 12.6 Hz, 1 H), 4.09-4.22 (m, 1 H), 4.32 (d, J = 13.2 Hz, 1 H), 7.83-7.97 (m, 3 H), 8.01-8.18 (m, 3 H), 8.27 (d, J = 8.7 Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J = 5.8 Hz, 1 H), 9.38 (s, 1 H); MS m/z 564 (M + H)⁺ m.p. 157.5° C. 154

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-8-(N,N-dimethylglycyl)-2- (4-isoquinolin-6-ylphenyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.71 (m, 4 H), 1.29-1.43 (m, 1 H), 1.43-1.62 (m, 2 H), 1.62-1.78 (m, 1 H), 1.87 (t, J = 9.8 Hz, 1 H), 2.21 (s, 6 H), 2.55-2.71 (m, 1 H), 2.96- 3.27 (m, 3 H), 3.43-3.62 (m, 2 H), 3.65-3.82 (m, 2 H), 3.88 (d, J = 7.3 Hz, 2 H), 4.06 (d, J = 13.5 Hz, 1 H), 4.15 (t, J = 8.2 Hz, 1 H), 4.27 (d, J = 12.8 Hz, 1 H), 7.82-7.99 (m, 3 H), 7.99-8.16 (m, 3 H), 8.27 (d, J = 8.7 Hz, 1 H), 8.39 (s, 1 H), 8.56 (d, J = 5.8 Hz, 1 H), 9.38 (s, 1 H); MS m/z 579 (M + H)⁺ m.p. 233.0° C. 171

8-(Cyclopropylcarbonyl)-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.61-0.76 (m, 2 H), 0.76-0.85 (m, 2 H), 0.86-0.99 (m, 2 H), 0.99-1.09 (m, 2 H), 1.36-2.17 (m, 9 H), 2.50 (s, 3 H), 2.89-3.99 (m, 8 H), 4.09- 4.34 (m, 1 H), 4.34-4.61 (m, 1 H), 6.45 (s, 1 H), 7.36-7.58 (m, 2 H), 7.59-7.74 (m, 3 H), 7.73-7.88 (m, 2 H); MS m/z 579 (M + H)⁺ m.p. 137.1° C. 172

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2-methyl-1- benzofuran-5-yl)phenyl]-8-(2- methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm ppm 0.64-0.80 (m, 2 H), 0.85-1.01 (m, 2 H), 1.03-1.25 (m, 10 H), 1.35- 2.12 (m, 6 H), 2.50 (s, 3 H), 2.72- 3.86 (m, 7 H), 3.86-4.06 (m, 1 H), 4.37-4.62 (m, 1 H), 6.44 (s, 1 H), 7.38-7.56 (m, 2 H), 7.58-7.73 (m, 3 H), 7.73-7.84 (m, 2 H); MS m/z 581 (M + H)⁺ m.p. 115.5 ° C. 174

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2- [4-(2-methyl-1-benzofuran-5- yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.55-0.78 (m, 2 H), 0.82-1.03 (m, 2 H), 1.35-1.73 (m, 4 H), 1.72-2.13 (m, 3 H), 2.31 (s, 6 H), 2.49 (s, 3 H), 2.89-3.87 (m, 11 H), 4.05-4.21 (m, 1 H), 4.30-4.55 (m, 1 H), 6.44 (s, 1 H), 7.38-7.56 (m, 2 H), 7.58-7.72 (m, 3 H), 7.72-7.83 (m, 2 H); MS m/z 596 (M + H)⁺ m.p. 90.3 ° C. 181

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 5.4 Hz, 4 H), 1.31- 1.94 (m, 6 H), 2.07 (s, 3 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.78-3.30 (m, 4 H), 3.32-3.60 (m, 4 H), 3.60-3.74 (m, 2 H), 3.77-3.93 (m, 1 H), 4.18-4.38 (m, 1 H), 7.68 (d, J = 8.7 Hz, 1 H), 7.75-7.89 (m, 2 H), 7.90-8.07 (m, 4 H); MS m/z 583 (M + H)⁺ m.p. 117.7 ° C. 182

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(N,N- dimethylglycyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 5.4 Hz, 4 H), 1.28- 1.97 (m, 7 H), 2.21 (s, 6 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.76-3.28 (m, 6 H), 3.34-3.61 (m, 3 H), 3.60-3.75 (m, 2 H), 3.95-4.14 (m, 1 H), 4.18- 4.37 (m, 1 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.75-7.90 (m, 2 H), 7.97 (d, J = 8.9 Hz, 4 H); MS m/z 626 (M + H)⁺ m.p. 107.9 ° C. 183

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(2- methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.71 (m, 4 H), 0.94-1.13 (m, 6 H), 1.28-1.99 (m, 6 H), 2.12-2.35 (m, 1 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.76-3.30 (m, 5 H), 3.33-3.78 (m, 5 H), 3.84-4.12 (m, 1 H), 4.19-4.43 (m, 1 H), 7.68 (d, J = 8.9 Hz, 1 H), 7.82 (dd, J = 8.0, 5.4 Hz, 2 H), 7.97 (d, J = 8.7 Hz, 4 H); MS m/z 611 (M + H)⁺ m.p. 136.4 ° C.

Example 8 (R)-3-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-8-(2-hydroxyethyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #127)

A mixture of (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.080 g, 0.157 mmol), 2-bromoethanol (0.056 mL, 0.785 mmol), and potassium carbonate (0.044 g, 0.314 mmol) in acetonitrile (5 mL) was heated at 65° C. overnight. The resulting mixture was allowed to cool to room temperature and was diluted with DCM (20 mL). The inorganic solids were filtered and the filtrate was concentrated yield a residue. The residue was purified by flash chromatography (silica gel, 0 to 100% of DCM:MeOH: 25% NH₄OH 9:0.9:0.1 in DCM). The fractions containing the desired product were concentrated to a sticky oil that was triturated with Et₂O to yield 3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one, as an off-white solid (0.042 g, 48%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.60-0.82 (m, 2H), 0.82-1.03 (m, 2H), 1.33-2.61 (m, 10H), 2.61-3.11 (m, 6H), 3.09-3.85 (m, 7H), 4.13 (s, 3H), 7.50 (d, J=8.7 Hz, 1H), 7.58-7.72 (m, 3H), 7.72-7.85 (m, 2H), 7.97 (s, 1H), 8.06 (s, 1H); MS m/z 555 (M+H)⁺; m.p. 99.6° C.;

Following the procedure described in Example 8, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 159

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-hydroxyethyl)-2-(4- isoquinolin-6-ylphenyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.76 (m, 2 H), 0.89-1.00 (m, 2 H), 1.37-1.71 (m, 4 H), 1.73-2.23 (m, 6 H), 2.23-2.58 (m, 1 H), 2.69 (t, J = 5.2 Hz, 2 H), 2.79 (t, J = 11.1 Hz, 2 H), 2.86-3.07 (m, 3 H), 3.14-3.39 (m, 1 H), 3.57-3.85 (m, 5 H), 7.67- 7.80 (m, 3 H), 7.88 (dd, J = 8.2, 3.8 Hz, 3 H), 7.99-8.17 (m, 2 H), 8.60 (d, J = 5.5 Hz, 1 H), 9.32 (br. s., 1 H); MS m/z 552 (M + H)⁺ 168

2-[4-(1-Benzofuran-5-yl)phenyl]-3- {[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-hydroxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.72 (m, 4 H), 1.41-2.00 (m, 7 H), 2.09-2.38 (m, 1 H), 2.52-2.64 (m, 2 H), 2.74-2.93 (m, 3 H), 3.02- 3.28 (m, 3 H), 3.39-3.72 (m, 7 H), 4.41 (br. s., 1 H), 7.04 (d, J = 1.8 Hz, 1 H), 7.63-7.82 (m, 4 H), 7.83-7.92 (m, 2 H), 8.03 (s, 1 H), 8.06 (d, J = 1.9 Hz, 1 H); MS m/z 514 (M + H)⁺ m.p. 105.7° C. 170

3-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-8-(2-hydroxyethyl)-2-[4- (1-methyl-1H-indazol-5-yl)phenyl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one MS m/z 541 (M + H)⁺ m.p. >300 °C. 173

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-hydroxyethyl)-2-[4-(2- methyl-1-benzofuran-5-yl)phenyl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CDCl₃) δ ppm 0.63-0.78 (m, 2 H), 0.94 (br. s., 2 H), 1.34-1.56 (m, 2 H), 1.70-2.46 (m, 7 H), 2.50 (s, 3 H), 2.58-3.10 (m, 6 H), 3.10-3.39 (m, 1 H), 3.38- 3.91 (m, 8 H), 6.44 (s, 1 H), 7.37- 7.56 (m, 2 H), 7.56-7.86 (m, 5 H); MS m/z 555 (M + H)⁺ m.p. 130.3° C. 185

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-hydroxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.72 (m, 4 H), 1.38 (br. s., 1 H), 1.81 (br. s., 2 H), 2.18-2.45 (m, 2 H), 2.57-2.72 (m, 1 H), 3.18-3.96 (m, 14 H), 4.11-4.21 (m, 1 H), 7.04 (d, J = 1.5 Hz, 1 H), 7.66-7.76 (m, 2 H), 7.76-7.86 (m, 2 H), 7.87-7.98 (m, 2 H), 8.00-8.11 (m, 2 H), 10.40 (br. s., 1 H); MS m/z 527 (M + H)⁺ m.p. 253.4° C.

Example 9 R)-2-(4-(1H-Indo)-5-yl)phenyl)-8-acetyl-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #147

STEP A: (R)-8-Acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

To a stirring solution of (R)-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.300 mg, 0.605 mmol) and Et₃N (0.252 mL, 1.82 mmol) in DCM (10 mL) was added acetyl chloride (0.065 mL, 0.908 mmol). After 1 h at room temperature, the resulting mixture was diluted with DCM (50 mL) and was washed with 0.5 M aqueous Na₂CO₃. The aqueous layer was extracted with additional DCM (10 mL) and the combined organic layers were dried over MgSO₄, filtered, and concentrated to yield a residue which was purified by flash chromatography on Silica gel using 0 to 4.7% MeOH/DCM. The resulting residue was triturated with di-isopropyl ether to yield (R)-8-acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one as a white solid (0.165 g, 53%).

MS m/z 501 (M+H)⁺.

STEP B: 8-Acetyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #147)

(R)-8-Acetyl-2-(4-bromophenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.075 g, 0.150 mmol), 5-indolylboronic acid (0.029 g, 0.180 mmol), 1.0M aqueous Na₂CO₃ (0.30 mL, 0.30 mmol) and 1,4-dioxane (2 mL) were combined and bubbled with nitrogen for 15 min. Bis(triphenylphosphine)palladium(II) chloride (0.006 g, 0.008 mmol) was added and the resulting mixture was heated to 85° C. for 2 h. The resulting mixture was cooled to room temperature, diluted with DCM (50 mL), and washed successively with water (15 mL) and saturated aqueous NaCl. The organic layer was dried over MgSO₄, filtered, and concentrated to yield a residue which was purified by flash chromatography (silica gel, 0 to 10% MeOH/DCM). The resulting residue was triturated with di-isopropyl ether to yield 8-acetyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-4-one, as a white solid, (0.040 g, 47%).

¹H NMR (300 MHz, DMSO-d6) δ ppm 0.52-0.72 (m, 4H), 1.28-1.95 (m, 6H), 2.07 (s, 3H), 2.13-2.39 (m, 1H), 2.86 (dd, J=11.7, 7.0 Hz, 0.5H), 3.01-3.30 (m, 3.5H), 3.37-3.62 (m, 3H), 3.62-3.75 (m, 2H), 3.75-3.93 (m, 1H), 4.15-4.40 (m, 1H), 6.52 (br. s., 1H), 7.40 (t, J=2.7 Hz, 1H), 7.44-7.56 (m, 2H), 7.71-7.81 (m, 2H), 7.82-7.90 (m, 2H), 7.93 (s, 1H), 11.21 (br. s., 1H); MS m/z 538 (M+H)⁺; m.p. 291.7° C.

Following the procedure described in Example 9, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 148

8-Acetyl-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 0.54-0.74 (m, 4 H), 1.31-1.96 (m, 6 H), 2.07 (s, 3 H), 2.12-2.41 (m, 1 H), 2.78- 2.96 (m, 0.5 H), 2.96-3.61 (m, 6.5 H), 3.67 (t, J = 6.9 Hz, 2 H), 3.76-3.94 (m, 1 H), 4.30 (d, J = 13.6 Hz, 1 H), 7.61-7.72 (m, 1 H), 7.71-7.86 (m, 3 H), 7.86-7.98 (m, 2 H), 8.03-8.33 (m, 2 H), 13.18 (s, 1 H) MS m/z 539 (M + H)⁺ m.p. 187.3° C. 129

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.68 (m, 4 H), 0.92-1.10 (m, 6 H), 1.27-1.90 (m, 5 H), 2.54-2.71 (m, 1 H), 2.84-3.01 (m, 1 H), 3.17 (t, J = 11.1 Hz, 1 H), 3.32-3.80 (m, 4 H), 3.88 (d, J = 7.3 Hz, 2 H), 3.98 (d, J = 13.3 Hz, 1 H), 4.15 (t, J = 8.2 Hz, 1 H), 4.32 (d, J = 12.4 Hz, 1 H), 6.92-7.15 (m, 1 H), 7.65-7.76 (m, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.99-8.14 (m, 2 H); MS m/z 553 (M + H)⁺ m.p. 237.2° C. 164

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2-[4- (1H-indol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.73 (m, 4 H), 1.27-1.96 (m, 7 H), 2.21 (s, 6 H), 2.23-2.40 (m, 1 H), 2.86 (dd, J = 11.5, 6.9 Hz, 0.5 H), 2.97-3.29 (m, 5 H), 3.41-3.61 (m, 2.5 H), 3.67 (t, J = 7.0 Hz, 2 H), 4.06 (d, J = 13.5 Hz, 1 H), 4.27 (d, J = 12.6 Hz, 1 H), 6.52 (br. s., 1 H), 7.37-7.45 (m, 1 H), 7.45-7.56 (m, 2 H), 7.70-7.82 (m, 2 H), 7.82-7.91 (m, 2 H), 7.93 (s, 1 H), 11.21 (br. s., 1 H); MS m/z 581 (M + H)⁺ m.p. 129.1° C. 165

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2-[4- (1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (br. s., 4 H), 1.24-2.02 (m, 7 H), 2.20 (br. s., 6 H), 2.24-2.39 (m, 1 H), 2.70-3.27 (m, 5 H), 3.39-3.60 (m, 4 H), 3.60-3.79 (m, 2 H), 4.06 (d, J = 12.6 Hz, 1 H), 4.28 (d, J = 12.6 Hz, 1 H), 7.57-7.71 (m, 1 H), 7.71-7.85 (m, 2 H), 7.85-8.00 (m, 2 H), 8.07-8.26 (m, 2 H), 13.03 (br. s., 1 H); MS m/z 582 (M + H)⁺ m.p. 176.4° C.

Example 10 (R)-2-(4-(Benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (Compound #116)

STEP A: (S)-tert-Butyl 3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate

(S)-tert-Butyl 3-((2-(4-bromophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)pyrrolidine-1-carboxylate (1.0 g, 2.1 mmol), benzofuran-5-ylboronic acid (0.52 g, 3.15 mmol), tetrakis(triphenylphosphine) palladium (0.073 g, 0.063 mmol), potassium carbonate (0.466 g, 4.4 mmol), DME (27 mL) and water (2.2 mL) were combined and the resulting mixture was heated to reflux for 16 h under argon atmosphere. The resulting mixture was concentrated concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 10% to 60% EtOAc in heptane) to yield (5)-tert-butyl 3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl) pyrrolidine-1-carboxylate (1.05 g, 98%).

¹H NMR (400 MHz, CDCl₃) δ ppm 1.41 (s, 9H), 1.74-1.85 (m, 1H), 1.88-1.99 (m, 3H), 1.99-2.13 (m, 6H), 2.26-2.40 (m, 1H), 2.81-2.95 (m, 1H), 3.13-3.24 (m, 1H), 3.24-3.32 (m, 1H), 3.33-3.43 (m, 1H), 3.61-3.77 (m, 2H), 6.85 (s, 1H), 7.54-7.63 (m, 2H), 7.65 (d, J=7.8 Hz, 2H), 7.69 (s, 1H), 7.75 (d, J=8.1 Hz, 2H), 7.85 (s, 1H); MS m/z 514.3 (M+H)⁺.

STEP B: (R)-2-(4-(Benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one

To a stirring solution of (S)-tert-butyl 3-((2-(4-(benzofuran-5-yl)phenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl) pyrrolidine-1-carboxylate (0.9 g, 1.75 mmol) in DCM (36 mL) was added TFA (9 mL). After stirring 2.5 h at room temperature under nitrogen the reaction mixture was concentrated to yield (R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one, as its corresponding TFA salt, as an oil, which was directly used directly into the next step.

MS m/z 414.1 (M+H)⁺.

STEP C: (R)-2-(4-(Benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (Compound #116)

To a stirring solution of (R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one TFA salt (41.3 mg, 0.1 mmol) in DCM (2.5 mL) and DIPEA (0.086 mL, 0.5 mmol) was added 1-methylcyclopropanecarbonyl chloride (0.014 mg, 0.12 mmol). After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo and the resulting residue was purified by flash chromatography (silica gel, 25% to 65% EtOAc in heptane) to yield (R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1-(1-methylcyclopropanecarbonyl) pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (36.5 mg, 74%).

¹H NMR (400 MHz, CDCl₃) δ ppm 0.44-0.55 (m, 2H), 0.78-1.01 (m, 2H), 1.19-1.24 (m, 3H), 1.38-1.64 (m, 2H), 1.78-2.02 (m, 4H), 2.02-2.13 (m, 4H), 2.30-2.44 (m, 1H), 3.08 (br. s., 1H), 3.26-3.54 (m, 2H), 3.53-3.84 (m, 2H), 6.85 (br. s., 1H), 7.53-7.63 (m, 2H), 7.66 (d, J=8.1 Hz, 2H), 7.69 (d, J=2.0 Hz, 1H), 7.76 (d, J=8.1 Hz, 2H), 7.84 (s, 1H); MS m/z 496.2 (M+H)⁺.

Following the procedure described in Example 10, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 119

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(3,3,3-trifluoropropanoyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 1.45- 1.68 (m, 1 H), 1.83-2.13 (m, 9 H), 2.31- 2.51 (m, 1 H), 3.00-3.16 (m, 3 H), 3.30- 3.49 (m, 2 H), 3.50-3.62 (m, 1 H), 3.62- 3.77 (m, 2 H), 6.85 (s, 1 H), 7.56 (d, J = 8.6 Hz, 1 H), 7.61 (d, J = 8.6 Hz, 1 H), 7.65 (d, J = 7.3 Hz, 2 H), 7.69 (s, 1 H), 7.73-7.80 (m, 2 H), 7.84 (s, 1 H); MS m/z 524.1 (M + H)⁺ 118

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(1-methyl-1H-pyrazol-3- yl)carbonyl]pyrrolidin-3-yl}methyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 1.42- 1.65 (m, 1 H), 1.79 (s, 2 H), 1.83-2.12 (m, 9 H), 2.34-2.49 (m, 1 H), 3.43-3.55 (m, 1 H), 3.61-3.81 (m, 3 H), 3.82 (s, 1 H), 3.90 (s, 2 H), 4.00 (dd, J = 11.7, 7.1 Hz, 1 H), 6.72 (dd, J = 8.6, 2.0 Hz, 1 H), 6.84 (s, 1 H), 7.30 (d, J = 2.0 Hz, 1 H), 7.50- 7.62 (m, 2 H), 7.62-7.70 (m, 3 H), 7.70- 7.76 (m, 2 H), 7.82 (d, J = 10.5 Hz, 1 H); MS m/z 522.2 (M + H)⁺ 117

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)- 1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CDCl₃) δ ppm 1.39- 1.51 (m, 1 H), 1.67-1.84 (m, 6 H), 1.88- 2.02 (m, 4 H), 2.02-2.12 (m, 4 H), 2.26- 2.39 (m, 1 H), 2.99 (dd, J = 10.4, 7.2 Hz, 1 H), 3.20-3.37 (m, 6 H), 3.63-3.78 (m, 2 H), 6.85 (s, 1 H), 7.53-7.63 (m, 2 H), 7.63-7.68 (m, 2 H), 7.69 (d, J = 2.0 Hz, 1 H), 7.75 (d, J = 8.3 Hz, 2 H), 7.84 (s, 1 H); MS m/z 511.2 (M + H)⁺ 189

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)- 1-(pyrrolidin-1-ylsulfonyl)pyrrolidin-3- yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.51-1.63 (m, 1 H), 1.84-1.90 (m, 4 H), 1.90-2.01 (m, 1 H), 2.01-2.16 (m, 4 H), 2.17-2.27 (m, 2 H), 2.28-2.38 (m, 2 H), 2.55 (dt, J = 14.0, 7.1 Hz, 1 H), 3.00 (dd, J = 10.0, 6.4 Hz, 1 H), 3.18-3.31 (m, 6 H), 3.35 (dd, J = 10.1, 7.0 Hz, 1 H), 3.93 (d, J = 7.3 Hz, 2 H), 6.87 (d, J = 1.2 Hz, 1 H), 7.58 (dd, J = 8.6, 1.7 Hz, 1 H), 7.63 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.2 Hz, 1 H), 7.84 (d, J = 8.6 Hz, 2 H), 7.86-7.91 (m, 3 H) MS m/z 547.2 (M + H)⁺  90

3-{[(3R)-1-Acryloylpyrrolidin-3-yl]methyl}- 2-[4-(1-benzofuran-5-yl)phenyl]-8-benzyl- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 1.40- 1.67 (m, 2 H), 1.76-2.02 (m, 2 H), 2.08- 2.24 (m, 2 H), 2.27-2.53 (m, 1 H), 2.62- 2.74 (m, 2 H), 2.84-2.94 (m, 2 H), 3.03- 3.16 (m, 1 H), 3.27-3.45 (m, 1 H), 3.45- 3.59 (m, 2 H), 3.59-3.77 (m, 4 H), 5.56- 5.70 (m, 1 H), 6.19-6.39 (m, 2 H), 6.79- 6.90 (m, 1 H), 7.23-7.30 (m, 1 H), 7.34 (t, J = 7.1 Hz, 2 H), 7.37-7.41 (m, 2 H), 7.55 (d, J = 8.6 Hz, 1 H), 7.61 (d, J = 8.6 Hz, 1 H), 7.63-7.67 (m, 2 H), 7.69 (d, J = 2.0 Hz, 1 H), 7.76 (dd, J = 8.1, 5.1 Hz, 2 H), 7.84 (s, 1 H); MS m/z 573.0 (M + H)⁺

Example 11 2-(4-(Benzofuran-5-yl)phenyl)-3-(((R)-1-((S)-tetrahydro-furan-2-carbonyl)pyrrolidin-3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (Compound #190)

To a stirring solution of (R)-2-(4-(benzofuran-5-yl)phenyl)-3-(pyrrolidin-3-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one (44 mg, 0.109 mmol) and tetrahydro-furan-2-carboxylic acid (12.9 mg, 0.109 mmol) in DCM (2.5 mL) and Et₃N (0.22 mL, 1.63 mmol) was added HATU (53.8 mg, 0.14 mmol). After stirring at room temperature overnight, the reaction mixture was concentrated in vacuo and the resulting residue was purified by flash chromatography (silica gel, 25% to 65% EtOAc in heptane) to yield 2-[4-(1-benzofuran-5-yl)phenyl]-3-({(3R)-1-[(2S)-tetrahydro-furan-2-ylcarbonyl]pyrrol idin-3-yl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one (36.7 mg, 66%).

¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43-1.70 (m, 1H), 1.81-2.11 (m, 9H), 2.11-2.32 (m, 4H), 2.38-2.62 (m, 1H), 3.11 (dd, J=12.2, 7.3 Hz, 1H), 3.28-3.44 (m, 1H), 3.49-3.65 (m, 2H), 3.77-3.96 (m, 4H), 4.37-4.47 (m, 1H), 6.86 (d, J=2.2 Hz, 1H), 7.56 (dd, J=8.8, 2.0 Hz, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.71 (d, J=2.2 Hz, 1H), 7.80-7.90 (m, 5H);

MS m/z 512.3 (M+H)⁺.

Following the procedure described in Example 11, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 191

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46-1.71 (m, 1 H), 1.84-2.14 (m, 9 H), 2.15-2.32 (m, 4 H), 2.51 (dt, J = 14.7, 7.1 Hz, 1 H), 3.09-3.21 (m, 1 H), 3.42 (dt, J = 11.1, 7.6 Hz, 1 H), 3.52-3.63 (m, 1 H), 3.63-3.77 (m, 1 H), 3.79-3.86 (m, 1 H), 3.86-3.97 (m, 3 H), 4.34-4.47 (m, 1 H), 6.86 (d, J = 1.2 Hz, 1 H), 7.56 (d, J = 8.6 Hz, 1 H), 7.59-7.64 (m, 1 H), 7.68- 7.73 (m, 1 H), 7.81-7.91 (m, 5 H); MS m/z 512.3 (M + H)⁺ 192

1-{[(3R)-3-({2-[4-(1-Benzofuran-5- yl)phenyl]-4-oxo-1,3-diazaspiro[4.4]non-1- en-3-yl}methyl)pyrrolidin-1- yl]carbonyl}cyclopropanecarbonitrile ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.42-1.63 (m, 3 H), 1.63-1.81 (m, 2 H), 1.99-2.16 (m, 5 H), 2.18-2.29 (m, 2 H), 2.29-2.41 (m, 2 H), 2.47-2.68 (m, 1 H), 3.16 (dd, J = 12.3, 7.2 Hz, 1 H), 3.39- 3.67 (m, 2 H), 3.82 (dt, J = 10.6, 7.5 Hz, 1 H), 3.89-4.06 (m, 3 H), 6.87 (d, J = 1.7 Hz, 1 H), 7.58 (dd, J = 8.6, 1.7 Hz, 1 H), 7.64 (d, J = 8.6 Hz, 1 H), 7.71 (d, J = 2.2 Hz, 1 H), 7.81-7.94 (m, 5 H); MS m/z 507.1 (M + H)⁺

Example 12 8-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #160)

and 8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #161)

STEP A: (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one, and (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one

10% Palladium on carbon (0.10 g) was added to a solution of 8-benzyl-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.635 g, 1.06 mmol) in MeOH (15 mL) under a nitrogen atmosphere. The reaction vessel was connected to a balloon filled with hydrogen and the vessel was evacuated and filled with hydrogen three times. After stirring under hydrogen overnight, HOAc (1 mL, 15.8 mmol) was added and the reaction again placed under hydrogen atmosphere and stirred for several days. The suspension was filtered through a pad of diatomaceous earth and the solids were washed three times with MeOH (20 mL). The combined filtrates were concentrated to dryness, then dissolved in DCM (30 mL) and washed with 1M aqueous NaOH (20 mL). The organic layer was dried over MgSO₄, filtered, and concentrated to yield a mixture of (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one and (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.506 g).

MS m/z 512 and 514 (M+H)⁺.

STEP B: 8-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #160), and 8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #161)

Acetyl chloride (0.283 mL, 3.98 mmol) was added to the mixture of (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one, and (R)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-2-(4-(1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one, prepared as described in Step A above, (0.406 g, 0.793 mmol) and Et₃N (1.12 mL, 8.00 mmol) in DCM (20 mL) at 0° C. The resulting mixture was allowed to warm to room temperature and MeOH (2 mL) was added after 30 min. DCM (20 mL) was added and the organic solution was washed once with 1M aq. NaOH. The organic layer was dried over MgSO₄, filtered, and concentrated; the resulting residue was filtered through a short pad of silica gel and eluted with 10% MeOH/DCM. Fractions containing the desired products were concentrated to yield a mixture that was further purified by reverse-phase HPLC using 10-46% CH₃CN/0.1% aq. TFA. Fractions containing a mixture of the desired products were combined, diluted with DCM (50 mL), and washed with 1M aq. NaOH. The organic layer was dried over MgSO₄, filtered, and concentrated. The resulting material was re-purified by flash chromatography (silica gel, 0-10% MeOH/DCM) to yield

(a) 8-Acetyl-2-[4-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.030 g).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.62-0.81 (m, 2H), 0.85-1.01 (m, 2H), 1.35-1.73 (m, 3H), 1.72-2.10 (m, 4H), 2.13-2.17 (m, 3H), 2.20 (d, J=2.2 Hz, 3H), 2.23-2.56 (m, 2H), 2.82-4.01 (m, 12H), 4.35-4.60 (m, 1H), 4.68 (s, 1H), 4.79 (s, 1H), 7.19-7.35 (m, 1H), 7.35-7.57 (m, 2H), 7.56-7.84 (m, 4H); MS m/z 596, m.p. 104.5° C.

(b) 8-Acetyl-2-[4-(2-acetyl-1,2,3,4,4a,8a-hexahydroisoquinolin-6-yl)phenyl]-3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.010 g).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.67-0.80 (m, 2H), 0.96 (d, J=3.8 Hz, 2H), 1.37-1.68 (m, 4H), 1.78-2.08 (m, 3H), 2.12 (s, 3H), 2.21 (d, J=2.1 Hz, 3H), 2.23-2.75 (m, 2H), 2.76-3.11 (m, 4H), 3.11-3.94 (m, 9H), 4.21-4.55 (m, 1H), 4.68 (s, 1H), 4.79 (s, 1H), 5.36-5.56 (m, 1H), 7.16-7.28 (m, 1H), 7.34-7.49 (m, 4H), 7.66 (d, J=6.7 Hz, 2H); MS m/z 598.

and (c) a mixture of the compound of (a) and the compound of (b); (0.120 g).

Example 13 3-{[(3R)-1-(Cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (Compound #163)

A mixture of 3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one (0.080 g, 0.158 mmol), acetone (0.0464 mL, 0.632 mmol), sodium triacetoxyborohydride (0.0403 g, 0.190 mmol), and AcOH (0.010 mL, 0.158 mmol) in THF (5 mL) was stirred at room temperature for 24 h. 1M aq. NaOH (5 mL) was added and the reaction mixture was extracted with DCM (2×10 mL). The combined organic layers were dried over MgSO₄, filtered, and concentrated. The resulting residue was purified by flash chromatography (silica gel, 0-10% of MeOH in DCM). Fractions containing desired product were concentrated and re-purified by reverse-phase HPLC using 30-73% 1:1 CH₃CN/MeOH in aq. 25 mM NH₄CO₃. Fractions containing desired product were concentrated, dissolved in MeOH (2 mL), and treated with 4N HCl in 1,4-dioxane (0.100 mL). The resulting solution was concentrated and the residue triturated with Et₂O, filtered, and dried under high vacuum to yield 3-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4-isoquinolin-6-ylphenyl)-8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec-1-en-4-one, dihydrochloride, as a white solid, (0.069 g, 70%).

¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J=3.6 Hz, 4H), 1.27-1.40 (m, 7H), 1.47-2.04 (m, 5H), 2.14-2.43 (m, 1H), 2.86 (dd, J=11.7, 7.3 Hz, 0.5H), 3.03-3.20 (m, 1H), 3.20-3.34 (m, 2.5H), 3.43-3.63 (m, 7H), 3.69 (t, J=7.3 Hz, 2H), 7.99 (dd, J=7.9, 5.2 Hz, 2H), 8.20 (dd, J=8.0, 3.8 Hz, 2H), 8.47 (d, J=8.8 Hz, 1H), 8.55 (d, J=6.5 Hz, 1H), 8.68 (d, J=8.7 Hz, 1H), 8.73 (d, J=6.6 Hz, 1H), 8.79 (s, 1H), 9.95 (s, 1H), 10.74-11.18 (m, 1H); MS m/z 550; m.p.>300° C.

Following the procedure described in Example 13, above, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art, the following compounds of formula (I) of the invention were prepared.

ID No. Structure Compound Name & Physical Data 162

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(1-methylethyl)-2-[4-(1- methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one dihydrochloride MS m/z 553 (M + H)⁺ 166

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(1-methylethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 525 (M + H)⁺ 167

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(1-methylethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.63- 0.76 (m, 2 H), 0.88-0.97 (m, 2 H), 1.14 (d, J = 6.5 Hz, 6 H), 1.36-1.74 (m, 4 H), 1.74-2.09 (m, 2 H), 2.06-2.56 (m, 4 H), 2.75-3.08 (m, 5 H), 3.12-3.36 (m, 1 H), 3.48-3.80 (m, 3 H), 6.85 (d, J = 1.8 Hz, 1 H), 7.51-7.57 (m, 1 H), 7.58-7.71 (m, 4 H), 7.71-7.80 (m, 2 H), 7.80-7.88 (m, 1 H); MS m/z 539 (M + H)⁺ 169

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(1-methylethyl)-2-[4-(1- methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 538 (M + H)⁺ m.p. 93.1° C. 184

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(1- methylethyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.69 (m, 4 H), 0.96-1.06 (m, 6 H), 1.41-1.94 (m, 6 H), 2.09-2.34 (m, 1 H), 2.34-2.39 (m, 3 H), 2.37 (s, 3 H), 2.50 (s, 3 H), 2.56-2.70 (m, 2 H), 2.70-2.91 (m, 2 H), 3.04-3.17 (m, 1 H), 3.26 (d, J = 4.9 Hz, 1 H), 3.33-3.59 (m, 1 H), 3.65 (t, J = 7.5 Hz, 2 H), 7.67 (d, J = 9.2 Hz, 1 H), 7.78 (dd, J = 7.8, 5.6 Hz, 2 H), 7.91-8.03 (m, 4 H); MS m/z 583 (M + H)⁺ m.p. 118.4° C. 186

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2-methyl-1-benzofuran-5- yl)phenyl]-8-(1-methylethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 4.5 Hz, 4 H), 1.16-2.06 (m, 13 H), 2.07-2.45 (m, 4 H), 2.76-3.27 (m, 4 H), 3.40-3.76 (m, 7 H), 6.66 (s, 1 H), 7.60 (s, 2 H), 7.72-7.84 (m, 2 H), 7.84- 7.97 (m, 3 H); MS m/z 553 (M + H)⁺ m.p. 143.1° C. 187

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]- 8-(1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (400 MHz, CDCl₃) δ ppm 0.69 (dd, J = 7.8, 3.2 Hz, 2 H), 0.84-0.94 (m, 2 H), 1.14 (d, J = 6.6 Hz, 6 H), 1.20-1.36 (m, 2 H), 1.64 (d, J = 12.8 Hz, 2 H), 1.98- 2.26 (m, 3 H), 2.63-3.05 (m, 5 H), 3.49- 3.63 (m, 1 H), 3.77-4.02 (m, 3 H), 4.09- 4.24 (m, 1 H), 6.63 (br. s., 1 H), 7.27- 7.33 (m, 1 H), 7.42-7.52 (m, 2 H), 7.61 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.90 (s, 1 H), 8.55 (br. s., 1 H); MS m/z 524 (M + H)⁺ 188

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.67 (m, 4 H), 1.02 (d, J = 6.3 Hz, 6 H), 1.23 (br. s., 1 H), 1.31-1.57 (m, 3 H), 1.85 (t, J = 9.9 Hz, 2 H), 2.54-2.70 (m, 3 H), 2.70-2.89 (m, 3 H), 3.65-3.81 (m, 2 H), 3.86 (d, J = 7.1 Hz, 2 H), 4.14 (t, J = 7.9 Hz, 1 H), 7.58-7.70 (m, 1 H), 7.75 (d, J = 8.0 Hz, 3 H), 7.90 (d, J = 8.0 Hz, 2 H), 8.16 (d, J = 4.7 Hz, 2 H), 13.17 (br. s., 1 H); MS m/z 525 (M + H)⁺ m.p. 162.6° C.

Example 14 5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one (Compound #49)

STEP A: tert-Butyl 3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate

To a stirring solution of 5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (9.9 g, 33.6 mmol) and tert-butyl 3-(bromomethyl)azetidine-1-carboxylate (12.6 g, 50.4 mmol) in DMF (180 mL) was added Cs₂CO₃ (36.5 g, 67.1 mmol). After stirring for 3 h at 80° C. under nitrogen, the reaction mixture was cooled and filtered through a pad of diatomaceous earth. The filtrate was concentrated and the residue was partitioned between EtOAc (250 mL) and water (150 mL). The organic phase was washed with brine, dried over MgSO₄, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 0-75% EtOAc in heptane) to yield tert-butyl 3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate (10.7 g, 73%); MS m/z 434 (M+H)⁺.

STEP B: 6-(Azetidin-3-ylmethyl)-5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

TFA (50 mL) was added to an ice-cold solution of tert-butyl 3-((5-(4-bromophenyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-6-yl)methyl)azetidine-1-carboxylate (10.7 g, 24.6 mmol) in DCM (100 mL). The solution was allowed to warm to room temperature and was stirred 1 h. The solution was concentrated in vacuo and the residue was co-evaporated twice with toluene (100 mL). The residue was pumped at high vacuum to yield 6-(azetidin-3-ylmethyl)-5-(4-bromophenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one TFA salt (20.3 g), which was used in the next step without purification; MS m/z 334 (M+H)⁺.

STEP C: 5-(4-Bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one

Cyclopropanecarbonyl chloride (2.46 mL, 27.1 mmol) was added dropwise to an ice cold solution of 5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (13.9 g, 24.6 mmol) and TEA (7.0 mL, 50.2 mmol) in DCM (100 mL). The resulting mixture was stirred 1 h and MeOH (2 mL) was added. The reaction mixture was diluted with DCM (150 mL) and washed successively with water (150 mL) and 1M aqueous Na₂CO₃ (150 mL). The organic layer was dried over MgSO₄ and concentrated in vacuo to yield a residue, which was purified by flash chromatography (silica gel, 0-5% MeOH in DCM) to give 5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one as an amorphous solid (7.66 g, 77%); MS m/z 402 (M+H)⁺.

STEP D: 5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one (Compound #49)

To a solution of 5-(4-bromophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one (7.66 g, 19.0 mmol) in acetonitrile (100 mL) was added 2-(benzofuran-5-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5.58 g, 22.9 mmol), aqueous 1.0M Na₂CO₃ (40 mL, 40 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.33 g, 0.48 mmol). The reaction mixture was bubbled with nitrogen for 5 min and heated at 85° C. for 2 h under nitrogen atmosphere. The resulting mixture was cooled to room temperature and partitioned between EtOAc (200 mL) and brine (50 mL). The aqueous layer was extracted with EtOAc (50 mL) and the combined organic layers were dried over MgSO₄ and concentrated in vacuo to yield a reddish oil. The reddish oil was purified by flash chromatography (silica gel, 0-5% MeOH in DCM) to yield a beige foam after concentration and pumping at high vacuum. The foam was crystallized from acetonitrile (30 mL) and washed with acetonitrile (3×10 mL) to yield 5-[4-(1-benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one as a light beige solid (5.70 g, 68%).

¹H NMR (300 MHz, CDCl₃) δ ppm 0.64-0.76 (m, 2H), 0.86-0.97 (m, 2H), 1.22-1.36 (m, 1H), 1.74-1.83 (m, 2H), 1.83-1.94 (m, 2H), 2.77-2.95 (m, 1H), 3.62 (dd, J=9.7, 5.6 Hz, 1H), 3.90-4.16 (m, 4H), 4.23 (t, J=8.2 Hz, 1H), 6.85 (d, J=2.1 Hz, 1H), 7.53-7.74 (m, 5H), 7.78 (d, J=8.4 Hz, 2H), 7.84-7.89 (m, 1H); MS m/z 440 (M+H)+; m.p. 181.3° C.

An additional batch of the compound of Example 14 was prepared, with measured physical properties as listed below.

ID No. Structure Compound Name & Physical Data 49

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3-yl]methyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one 1H NMR (300 MHz, CDCl₃) δ ppm 0.64- 0.76 (m, 2 H), 0.86-0.97 (m, 2 H), 1.22- 1.36 (m, 1 H), 1.74-1.83 (m, 2 H), 1.83- 1.94 (m, 2 H), 2.77-2.95 (m, 1 H), 3.62 (dd, J = 9.7, 5.6 Hz, 1 H), 3.90-4.16 (m, 4 H), 4.23 (t, J = 8.2 Hz, 1 H), 6.85 (d, J = 2.1 Hz, 1 H), 7.53-7.74 (m, 5 H), 7.78 (d, J = 8.4 Hz, 2 H), 7.84-7.89 (m, 1 H); MS m/z 440 (M + H)⁺ m.p. 182.0° C.

Additional representative compounds of formula (I) of the present invention were prepared according to the procedures as described in the general synthesis schemes and examples detailed herein, selecting and substituting the appropriate reagents, starting materials, and purification methods, and adjusting reaction temperatures, times and other variables or parameters, as needed or desirable, as would be readily recognized by those skilled in the art. Measured physical properties for said compounds were as listed below.

ID No. Structure Compound Name & Physical Data  44

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-{4-[6-(4-methylpiperazin-1- yl)pyridin-3-yl]phenyl}-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 541.3 (M + H)⁺  95

2-[(3R)-3-({2-[4-(1-Benzofuran-5- yl)phenyl]-8-benzyl-4-oxo-1,3,8- triazaspiro[4.5]dec-1-en-3- yl}methyl)pyrrolidin-1-yl]acetamide MS m/z 576.0 (M + H)+  96

2-[4-(1-Benzofuran-5-yl)phenyl]-8-benzyl- 3-{[(3R)-1-(2-cyclopropyl-2- oxoethyl)pyrrolidin-3-yl]methyl}-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 600.9 (M + H)+ 200

(R)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-5-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.84-0.94 (m, 2 H), 1.09 (d, J = 9.6 Hz, 1 H), 1.22 (br. s., 1 H), 1.49 (d, J = 11.1 Hz, 1 H), 1.75-1.80 (m, 2 H), 1.84-1.98 (m, 3 H), 2.45 (dt, J = 14.1, 7.1 Hz, 1 H), 2.87 (br. s., 0.5 H), 3.09 (br. s., 1 H), 3.38 (br. s., 0.5 H), 3.52 (br. s., 1.5 H), 3.64 (br. s., 0.5 H), 3.80 (d, J = 6.6 Hz, 3 H), 4.09-4.15 (m, 3 H), 7.50 (d, J = 9.1 Hz, 1 H), 7.68 (d, J = 7.6 Hz, 3 H), 7.78 (d, J = 8.6 Hz, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H) MS m/z 484.1 (M + H)+ 201

(R)-5-(4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.44-0.55 (m, 2 H), 0.78-0.86 (m, 1 H), 0.91 (d, J = 9.1 Hz, 1 H), 1.22 (s, 3 H), 1.60 (br. s., 1 H), 1.68 (br. s., 1 H), 1.74-1.81 (m, 2 H), 1.84-1.98 (m, 3 H), 2.46 (dt, J = 14.4, 7.5 Hz, 1 H), 3.09 (br. s., 1 H), 3.34 (br. s., 0.5 H), 3.48 (br. s., 1.5 H), 3.65 (br. s., 1 H), 3.82 (br. s., 2 H), 4.13 (s, 3 H), 7.50 (d, J = 8.6 Hz, 1 H), 7.68 (d, J = 7.6 Hz, 3 H), 7.75-7.81 (m, 2 H), 7.97 (s, 1 H), 8.06 (s, 1 H). MS m/z 482.2 (M + H)⁺ 202

(R)-5-(4′-chloro-2′-fluoro-[1,1′-biphenyl]-4- yl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.92 (br. s., 2 H), 1.12 (br. s., 2 H), 1.73-1.81 (m, 2 H), 1.83-1.98 (m, 3 H), 2.44 (dt, J = 14.1, 7.1 Hz, 1 H), 2.60 (d, J = 18.2 Hz, 1 H), 2.69 (br s, 1 H), 2.74 (br. s., 1 H), 2.99 (d, J = 13.1 Hz, 1 H), 3.10 (d, J = 14.7 Hz, 1 H), 3.39 (br. s., 1 H), 3.52 (br. s., 1 H), 3.65 (br. s., 1 H), 3.79 (d, J = 7.1 Hz, 3 H), 7.19-7.26 (m, 3 H), 7.41 (q, J = 8.6 Hz, 2 H), 7.61 (d, J = 7.1 Hz, 1 H), 7.89 (d, J = 8.6 Hz, 1 H). MS m/z 482.2 (M + H)+ 203

(R)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-5-(4-(6-methoxynaphthalen- 2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.88 (br. s., 2 H), 1.07 (br. s., 2 H), 1.49 (br. s., 1 H), 1.74-1.80 (m, 2 H), 1.84-1.97 (m, 3 H), 2.44 (dt, J = 14.0, 6.9 Hz, 1 H), 3.10 (br. s., 1 H), 3.32 (br. s., 1 H), 3.51 (br. s., 1.5 H), 3.59-3.72 (m, 1 H), 3.80 (d, J = 6.6 Hz, 2.5 H), 3.95 (s, 3 H), 7.15-7.23 (m, 2 H), 7.69 (d, J = 8.6 Hz, 2 H), 7.74 (d, J = 8.6 Hz, 1 H), 7.79- 7.87 (m, 4 H), 8.03 (s, 1 H). MS m/z 510.4 (M + H)+ 204

5-(4-(1-methyl-1H-indazol-5-yl)phenyl)-6- (((3R)-1-(oxetane-2-carbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44-1.57 (m, 1 H), 1.73-1.81 (m, 2 H), 1.87 (d, J = 3.0 Hz, 2 H), 1.90-1.99 (m, 1 H), 2.46 (dt, J = 13.6, 6.8 Hz, 1 H), 2.68-2.84 (m, 1 H), 2.86-3.04 (m, 1 H), 3.05-3.23 (m, 1 H), 3.24-3.33 (m, 0.5 H), 3.33-3.45 (m, 1 H), 3.46-3.66 (m, 1.5 H), 3.74-3.87 (m, 2 H), 4.13 (s, 3 H), 4.48-4.59 (m, 1 H), 4.59-4.70 (m, 1 H), 5.04-5.21 (m, 1 H), 7.50 (d, J = 8.6 Hz, 1 H), 7.64-7.72 (m, 3 H), 7.77 (d, J = 8.6 Hz, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H). MS m/z 484.4 (M + H)+ 205

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(tetrahydro-furan-2- carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.55-1.64 (m, 2 H), 1.64-1.83 (m, 5 H), 1.86-1.99 (m, 1 H), 2.36 (s, 3 H), 2.56- 2.66 (m, 1 H), 3.36-3.44 (m, 1 H), 3.59- 3.74 (m, 5 H), 3.74-3.84 (m, 1 H), 4.10 (s, 3 H), 4.11-4.23 (m, 2 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.67-7.87 (m, 4 H), 8.13 (d, J = 2.9 Hz, 2 H). MS m/z 498.3 (M + H)+ 206

(S)-5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(tetrahydro-furan-2- carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d6) δ ppm 1.56-1.64 (m, 2 H), 1.64-1.85 (m, 5 H), 1.86-1.99 (m, 1 H), 2.36 (s, 3 H), 2.61 (d, J = 4.9 Hz, 1 H), 3.35-3.44 (m, 1 H), 3.59-3.74 (m, 5 H), 3.74-3.85 (m, 1 H), 4.10 (s, 3 H), 4.12-4.23 (m, 2 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.68-7.85 (m, 4 H), 8.11-8.17 (m, 2 H). MS m/z 498.2 (M + H)+ 207

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.11 (d, J = 2.2 Hz, 2 H), 0.51 (s, 2 H), 0.83 (s, 3 H), 1.29-1.40 (m, 2 H), 1.48- 1.58 (m, 2 H), 2.12 (s, 3 H), 2.29-2.42 (m, 1 H), 3.13-3.39 (m, 2 H), 3.39-3.50 (m, 2 H), 3.55-3.75 (m, 2 H), 3.85 (s, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.43-7.62 (m, 4 H), 7.88 (s, 2 H). MS m/z 482.3 (M + H)+ 208

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclobutanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.14 (s, 3 H), 1.45-1.63 (m, 5 H), 1.71- 1.89 (m, 3 H), 2.02-2.29 (m, 2 H), 2.36 (s, 3 H), 2.58 (br. s., 1 H), 3.34-3.47 (m, 2 H), 3.53-3.67 (m, 1 H), 3.75 (d, J = 15.1 Hz, 2 H), 4.00 (t, J = 8.4 Hz, 1 H), 4.10 (s, 3 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.67-7.84 (m, 4 H), 8.13 (s, 2 H). MS m/z 496.3 (M + H)+ 209

(R)-5-(3′-chloro-4′-fluoro- [1,1′-biphenyl]-4-yl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 6.7 Hz, 4 H), 1.33-1.66 (m, 4 H), 1.69-1.93 (m, 3 H), 2.25 (d, J = 7.0 Hz, 1 H), 2.88 (dd, J = 11.8, 6.9 Hz, 1 H), 3.09-3.19 (m, 1 H), 3.19-3.30 (m, 1 H), 3.40-3.62 (m, 1 H), 3.75 (t, J = 6.4 Hz, 2 H), 7.56 (t, J = 8.9 Hz, 1 H), 7.81 (dd, J = 8.3, 4.2 Hz, 3 H), 7.90 (dd, J = 8.4, 2.2 Hz, 2 H), 8.01 (d, J = 7.0 Hz, 1 H). MS m/z 466 (M + H)+ 210

(S)-5-(4-(1H-indol-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.75 (m, 4 H), 1.35-1.69 (m, 4 H), 1.69-1.97 (m, 3 H), 2.20-2.35 (m, 1 H), 2.92 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06- 3.21 (m, 1 H), 3.21-3.31 (m, 1 H), 3.42- 3.66 (m, 1.5 H), 3.77 (t, J = 6.7 Hz, 2 H), 6.52 (d, J = 2.9 Hz, 1 H), 7.41 (d, J = 3.0 Hz, 1 H), 7.44-7.55 (m, 2 H), 7.77 (dd, J = 8.2, 3.7 Hz, 2 H), 7.86 (d, J = 8.1 Hz, 2 H), 7.94 (s, 1 H), 11.09 (br. s., 1 H). MS m/z 453 (M + H)+ 211

(S)-5-(4-(benzo[b]thiophen-5-yl)phenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.32-0.50 (m, 4 H), 1.11-1.44 (m, 4 H), 1.46-1.72 (m, 3 H), 1.97-2.12 (m, 1 H), 2.67 (dd, J = 11.8, 6.9 Hz, 0.5 H), 2.84- 2.98 (m, 1 H), 2.98-3.07 (m, 1 H), 3.18- 3.40 (m, 1.5 H), 3.54 (t, J = 6.5 Hz, 2 H), 7.32 (d, J = 5.5 Hz, 1 H), 7.47-7.65 (m, 4 H), 7.65-7.76 (m, 2 H), 7.90 (d, J = 8.5 Hz, 1 H), 8.05 (s, 1 H). MS m/z 470 (M + H)+ 212

(R)-2-(5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-1H-indol-3- yl)acetonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 6.7 Hz, 4 H), 1.52-1.69 (m, 4 H), 1.70-1.97 (m, 3 H), 2.29 (br. s., 0.5 H), 2.38 (br. s., 0.5 H), 2.84-3.00 (m, 0.5 H), 3.19 (br. s., 1 H), 3.41 (br. s., 0.5 H), 3.45-3.66 (m, 2 H), 3.78 (t, J = 7.1 Hz, 2 H), 4.13 (s, 2 H), 7.43 (s, 1 H), 7.47-7.61 (m, 2 H), 7.73-7.85 (m, 2 H), 7.85-7.95 (m, 2 H), 8.02 (s, 1 H), 11.26 (br. s., 1 H). MS m/z 492 (M + H)+ 213

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethyl-1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.66 (br. s., 4 H), 1.60 (br. s., 4 H), 1.79 (br. s., 3 H), 2.23 (s, 3 H), 2.35 (br. s., 3 H), 2.37-2.47 (m, 1 H), 2.93 (br. s., 0.5 H), 3.16 (br. s., 1 H), 3.28 (br. s., 1 H), 3.50 (br. s., 1.5 H), 3.78 (br. s., 2 H), 7.28- 7.47 (m, 2 H), 7.75 (br. s., 3 H), 7.87 (d, J = 7.3 Hz, 2 H), 10.79 (br. s., 1 H). MS m/z 481 (M + H)+ 214

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2-methyl-1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.78 (m, 4 H), 1.60 (br. s., 4 H), 1.78 (br. s., 3 H), 2.29 (br. s., 1 H), 2.42 (s, 3 H), 2.92 (br. s., 0.5 H), 3.07-3.21 (m, 1 H), 3.27 (br. s., 1 H), 3.48 (br. s., 1.5 H), 3.78 (br. s., 2 H), 6.22 (br. s., 1 H), 7.39 (br. s., 2 H), 7.83 (s, 3 H), 7.79 (s, 2 H), 11.04 (br. s., 1 H). MS m/z 467 (M + H)+ 215

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(1-methyl-1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 5.8 Hz, 4 H), 1.43 (d, J = 19.0 Hz, 1 H), 1.50-1.69 (m, 3 H), 1.79 (d, J = 3.8 Hz, 2 H), 1.88 (d, J = 6.3 Hz, 1 H), 2.29 (br. s., 1 H), 2.92 (d, J = 4.8 Hz, 0.5 H), 3.08-3.21 (m, 1 H), 3.21-3.31 (m, 1 H), 3.44-3.58 (m, 1.5 H), 3.78 (t, J = 6.7 Hz, 2 H), 3.84 (s, 3 H), 6.52 (d, J = 2.6 Hz, 1 H), 7.39 (d, J = 2.7 Hz, 1 H), 7.57 (s, 2 H), 7.72-7.82 (m, 2 H), 7.82-7.91 (m, 2 H), 7.95 (s, 1 H). MS m/z 467 (M + H)+ 216

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2-(hydroxymethyl)-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (d, J = 5.8 Hz, 4 H), 1.46 (dd, J = 12.5, 7.3 Hz, 1 H), 1.57-1.72 (m, 3 H), 1.73- 1.84 (m, 2 H), 1.84-1.98 (m, 1 H), 2.31 (t, J = 7.0 Hz, 0.5 H), 2.43 (d, J = 13.7 Hz, 0.5 H), 2.83-3.00 (m, 0.5 H), 3.09-3.23 (m, 1 H), 3.24-3.34 (m, 1 H), 3.40-3.59 (m, 1.5 H), 3.74-3.91 (m, 2 H), 4.67 (d, J = 5.5 Hz, 2 H), 5.32 (t, J = 5.6 Hz, 1 H), 6.40 (s, 1 H), 7.43-7.52 (m, 2 H), 7.74- 7.84 (m, 2 H), 7.88 (d, J = 7 .7 Hz, 3 H), 11.18 (s, 1 H). MS m/z 483 (M + H)+ 217

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(3-(2-hydroxyethyl)-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR 300 MHz, DMSO-d₆) δ ppm 0.51-0.75 (m, 4 H), 1.35-1.54 (m, 1 H), 1.54-1.68 (m, 3 H), 1.70-1.81 (m, 2 H), 1.81-1.96 (m, 1 H), 2.22-2.47 (m, 1 H), 2.85-3.01 (m, 2.5 H), 3.08-3.22 (m, 1 H), 3.22-3.32 (m, 1 H), 3.41-3.63 (m, 1.5 H), 3.65-3.74 (m, 2 H), 3.78 (t, J = 7.2 Hz, 2 H), 4.64 (t, J = 5.4 Hz, 1 H), 7.15- 7.28 (m, 1 H), 7.39-7.53 (m, 2 H), 7.72- 7.82 (m, 2 H), 7.82-7.97 (m, 3 H), 10.93 (s, 1 H). MS m/z 497 (M + H)+ 218

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(1,3-dimethyl-1H-indazol- 5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.72 (dd, J = 7.7, 3.0 Hz, 2 H), 0.87- 1.03 (m, 2 H), 1.46-1.58 (m, 1 H),1.68- 1.75 (m, 1 H), 1.75-1.83 (m, 2 H), 1.84- 1.92 (m, 2 H), 2.02 (d, J = 6.0 Hz, 1 H), 2.37-2.52 (m, 1 H), 2.65 (s, 3 H), 3.07 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.23-3.40 (m, 1 H), 3.48-3.75 (m, 2.5 H), 3.75- 3.93 (m, 2 H), 4.06 (s, 3 H), 7.44 (d, J = 8.7 Hz, 1 H), 7.64-7.74 (m, 3 H), 7.76- 7.85 (m, 2 H), 7.90 (s, 1 H). MS m/z 482 (M + H)+ 219

(R)-5-(4-(3-aminoisoquinolin-6-yl)phenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.66-0.80 (m, 2 H), 0.88-1.05 (m, 2 H), 1.41-1.60 (m, 2 H), 1.60-1.85 (m, 2 H), 1.85-1.94 (m, 2 H), 1.94-2.10 (m, 1 H), 2.36-2.52 (m, 0.5 H), 2.52-2.68 (m, 0.5 H), 3.07 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.21-3.42 (m, 1 H), 3.51-3.73 (m, 2.5 H), 3.75-3.94 (m, 2 H), 4.55 (br. s., 2 H), 6.81 (s, 1 H), 7.53 (d, J = 8.5 Hz, 1 H), 7.67-7.81 (m, 3 H), 7.81-7.96 (m, 3 H), 8.92 (s, 1 H). MS m/z 480 (M + H)+ 220

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(3-fluoroisoquinolin-6- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.90-1.04 (m, 2 H), 1.52 (qd, J = 8.2, 4.2 Hz, 1 H), 1.77- 1.85 (m, 3 H), 1.85-1.93 (m, 2 H), 1.93- 2.10 (m, 1 H), 2.44 (dt, J = 14.3, 7.2 Hz, 1 H), 3.05 (dd, J = 12.0, 7.2 Hz, 0.5 H), 3.23- 3.41 (m, 1 H), 3.43-3.62 (m, 2 H), 3.62- 3.82 (m, 1.5 H), 3.82-3.90 (m, 1 H), 7.33 (s, 1 H), 7.73-7.81 (m, 2 H), 7.81- 7.93 (m, 3 H), 8.05 (s, 1 H), 8.12 (d, J = 8.7 Hz, 1 H), 9.02 (s, 1 H). MS m/z 483 (M + H)+ 221

(R)-6-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-1-methyl-1H-indazole- 3-carboxamide ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.81 (m, 2 H), 0.87-1.06 (m, 2 H), 1.46-1.58 (m, 1 H), 1.66 (d, J = 7.6 Hz, 1 H), 1.75-1.84 (m, 2 H), 1.84-1.93 (m, 2 H), 2.01 (d, J = 12.0 Hz, 1 H), 2.44 (br. s., 1 H), 3.07 (dd, J = 11.9, 7.1 Hz, 0.5 H), 3.22-3.41 (m, 1 H), 3.49-3.68 (m, 2.5 H), 3.75-3.95 (m, 2 H), 4.17 (s, 3 H), 5.55 (br. s., 1 H), 6.92 (br. s., 1 H), 7.54 (d, J = 8.8 Hz, 1 H), 7.66-7.80 (m, 3 H), 7.85 (dd, J = 8.0, 4.9 Hz, 2 H), 8.65 (s, 1 H). MS m/z 511 (M + H)+ 222

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.66-0.76 (m, 2 H), 0.91 (t, J = 3.8 Hz, 2 H), 1.31 (dq, J = 8.3, 4.0 Hz, 1 H), 1.77-1.87 (m, 2 H), 1.88-1.97 (m, 2 H), 2.80-2.98 (m, 1 H), 3.56 (dd, J = 9.8, 5.6 Hz, 1 H), 3.75-3.88 (m, 1 H), 3.98 (q, J = 9.3 Hz, 3 H), 4.28 (t, J = 8.3 Hz, 1 H), 7.61 (d, J = 11.0 Hz, 1 H), 7.67-7.75 (m, 3 H), 7.85-7.93 (m, 1 H), 7.98-8.09 (m, 2 H), 8.15 (s, 1 H), 8.31 (s, 1 H). MS m/z 493 (M + H)+ 223

5-(4-(6-fluoronaphthalen-2-yl)-2- methylphenyl)-6-((1-(oxetane-2- carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.70 (d, J = 4.9 Hz, 4 H), 1.79 (br. s., 2 H), 2.35 (s, 3 H), 2.58-2.72 (m, 1 H), 2.79 (d, J = 15.1 Hz, 1 H), 3.38-3.50 (m, 1 H), 3.50-3.81 (m, 3 H), 3.82-4.07 (m, 1.5 H), 4.09-4.32 (m, 1 H), 4.37-4.63 (m, 1 H), 4.95-5.12 (m, 0.5 H), 7.20- 7.30 (m, 1 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.39-7.48 (m, 1 H), 7.55-7.65 (m, 2 H), 7.67-7.77 (m, 1 H), 7.77-7.90 (m, 2 H), 8.00 (s, 1 H). MS m/z 498.2 (M + H)+ 224

6-(3-methyl-4-(6-((1-(oxetane-2- carbonyl)azetidin-3-yl)methyl)-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2- naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.80 (d, J = 6.3 Hz, 3 H), 1.85-1.93 (m, 2 H), 2.46 (s, 3 H), 2.68-2.81 (m, 1 H), 2.87 (d, J = 4.0 Hz, 1 H), 3.59-3.90 (m, 4 H), 3.91-4.16 (m, 2 H), 4.19-4.42 (m, 1 H), 4.47-4.71 (m, 1.5 H), 5.06- 5.18 (m, 0.5 H), 7.48 (d, J = 7.7 Hz, 1 H), 7.65-7.75 (m, 3 H), 7.85-7.95 (m, 1 H), 8.02 (dd, J = 8.4, 3.4 Hz, 2 H), 8.14 (s, 1 H), 8.30 (s, 1 H). MS m/z 505 (M + H)+ 225

6-(3-fluoro-4-(6-((1-(1- fluorocyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.08-1.21 (m, 2 H), 1.30 (d, J = 8.9 Hz, 2 H), 1.78-1.88 (m, 2 H), 1.88-1.97 (m, 2 H), 2.89-3.01 (m, 1 H), 3.66 (d, J = 4.5 Hz, 1 H), 3.81-4.00 (m, 2 H), 4.09 (d, J = 9.3 Hz, 2 H), 4.45 (br. s., 1 H), 7.62 (d, J = 10.9 Hz, 1 H), 7.66-7.77 (m, 3 H), 7.85-7.94 (m, 1 H), 8.05 (t, J = 7.8 Hz, 2 H), 8.16 (s, 1 H), 8.32 (s, 1 H). MS m/z 511.2 (M + H)+ 226

6-(3-fluoro-4-(6-((1-(oxetane-2- carbonyl)azetidin-3-yl)methyl)-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)phenyl)-2- naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.73-1.85 (m, 2 H), 1.89 (br. s., 2 H), 2.67-3.00 (m, 3 H), 3.59-3.70 (m, 1 H), 3.73-3.96 (m, 2.5 H), 3.99-4.11 (m, 1.5 H), 4.25 (t, J = 8.9 Hz, 1 H), 4.45-4.69 (m, 2 H), 5.05-5.16 (m, 1 H), 7.54-7.63 (m, 1 H), 7.65-7.73 (m, 3 H), 7.83-7.91 (m, 1 H), 7.97-8.08 (m, 2 H), 8.13 (s, 1 H), 8.29 (s, 1 H). MS m/z 509.3 (M + H)+ 227

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2-methyl-2H- indazol-6-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61-0.74 (m, 2 H), 0.89 (quin, J = 3.6 Hz, 2 H), 1.21-1.34 (m, 1 H), 1.73- 1.83 (m, 2 H), 1.83-1.94 (m, 2 H), 2.78- 2.94 (m, 1 H), 3.58 (dd, J = 9.8, 5.7 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H), 3.86-4.05 (m, 3 H), 4.17-4.33 (m, 4 H), 7.31-7.38 (m, 1 H), 7.52 (d, J = 11.0 Hz, 1 H), 7.56- 7.66 (m, 2 H), 7.76 (d, J = 8.7 Hz, 1 H), 7.93 (d, J = 4.8 Hz, 2 H). MS m/z 272.2 (M + H)+ 228

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6-fluoroquinolin- 2-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.60-0.72 (m, 2 H), 0.86 (quin, J = 3.6 Hz, 2 H), 1.26 (td, J = 8.1, 3.9 Hz, 1 H), 1.73-1.84 (m, 2 H), 1.84-1.93 (m, 2 H), 2.73-2.91 (m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1 H), 3.70-3.82 (m, 1 H), 3.85- 4.01 (m, 3 H), 4.22 (t, J = 8.3 Hz, 1 H), 7.41-7.58 (m, 2 H), 7.67 (t, J = 7.6 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 1 H), 8.02-8.20 (m, 3 H), 8.23 (d, J = 8.7 Hz, 1 H). MS m/z 487.2 (M + H)+ 229

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-fluorophenyl)quinoline-2- carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.68 (dd, J = 6.8, 4.2 Hz, 2 H), 0.88 (t, J = 3.6 Hz, 2 H), 1.26-1.36 (m, 1 H), 1.74- 1.85 (m, 2 H), 1.85-1.96 (m, 2 H), 2.76- 2.99 (m, 1 H), 3.54 (d, J = 5.5 Hz, 1 H), 3.80 (d, J = 6.6 Hz, 1 H), 3.86-4.07 (m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.60 (d, J = 10.9 Hz, 1 H), 7.64-7.73 (m, 2 H), 7.77 (d, J = 8.4 Hz, 1 H), 8.03-8.17 (m, 2 H), 8.30 (d, J = 8.7 Hz, 1 H), 8.39 (d, J = 8.5 Hz, 1 H). MS m/z 494 (M + H)+ 230

(R)-5-(4-(benzo[b]thiophen-5-yl)-3- methylphenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.77 (m, 2 H), 0.79-1.00 (m, 2 H), 1.39-1.53 (m, 1 H), 1.65-1.75 (m, 2 H), 1.76-1.87 (m, 2 H), 1.89-2.04 (m, 1 H), 2.28 (s, 3 H), 2.44-2.60 (m, 1 H), 3.00 (dd, J = 11.8, 7.1 Hz, 0.5 H), 3.14- 3.33 (m, 1 H), 3.36-3.61 (m, 3.5 H), 3.69- 3.86 (m, 2 H), 7.17-7.40 (m, 4 H), 7.40- 7.57 (m, 2 H), 7.70 (s, 1 H), 7.87 (d, J = 8.1 Hz, 1 H). MS m/z 484 (M + H)+ 231

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3- dimethylbenzo[b]thiophen-5-yl)-3- methylphenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (br. s., 4 H), 1.47 (d, J = 7.4 Hz, 1 H), 1.61 (br. s., 2 H), 1.66 (br. s., 0.5 H), 1.79 (d, J = 3.8 Hz, 2 H), 1.89 (d, J = 5.5 Hz, 0.5 H), 2.32 (d, J = 8.5 Hz, 6 H), 2.45 (br s, 1 H), 2.50 (br. s., 3 H), 2.87-3.00 (m, 0.5 H), 3.10-3.23 (m, 1 H), 3.29 (br. s., 1 H), 3.44-3.58 (m, 2.5 H), 3.71-3.87 (m, 2 H), 7.31 (d, J = 8.1 Hz, 1 H), 7.44 (d, J = 7.8 Hz, 1 H), 7.62 (br. s., 3 H), 7.93 (d, J = 8.1 Hz, 1 H). MS m/z 512 (M + H)+ 232

(R)-5-(4-(benzofuran-5-yl)-3- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (br. s., 4 H), 1.45 (br s., 0.5H), 1.63 (br. s., 3.5 H), 1.76-1.85 (m, 2 H), 1.90 (br s., 1 H), 2.22-2.45 (m, 1 H), 2.88- 2.95 (m, 0.5 H), 3.19 (d, J = 5.9 Hz, 1 H), 3.60 (br. s., 2.5 H), 3.78 (br. s., 2 H), 7.06 (br. s., 1 H), 7.56 (d, J = 8.4 Hz, 1 H), 7.61- 7.81 (m, 4 H), 7.92 (br. s., 1 H), 8.08 (s, 1 H). MS m/z 472 (M + H)+ 233

(R)-5-(4-(benzo[b]thiophen-5-yl)-3- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65 (dd, J = 7.6, 3.1 Hz, 2 H), 0.83- 0.95 (m, 2 H), 1.44 (td, J = 8.0, 4.3 Hz, 1 H), 1.63 (dd, J = 12.6, 7.8 Hz, 1 H), 1.69- 1.76 (m, 2 H), 1.76-1.84 (m, 2 H), 1.84- 2.01 (m, 1 H), 2.28-2.58 (m, 1 H), 3.01 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.15-3.34 (m, 1 H), 3.43-3.83 (m, 4.5 H), 7.34 (d, J = 5.4 Hz, 1 H), 7.36-7.53 (m, 4 H), 7.54- 7.66 (m, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.97 (s, 1 H). MS m/z 488 (M + H)+ 234

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-fluoro-4-(1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65 (dd, J = 7.8, 3.0 Hz, 2 H), 0.83- 0.97 (m, 2 H), 1.41-1.51 (m, 1 H), 1.55- 1.68 (m, 1 H), 1.68-1.76 (m, 2 H), 1.76- 1.84 (m, 2 H), 1.84-1.91 (m, 1 H), 2.29- 2.58 (m, 1 H), 3.02 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.14-3.35 (m, 1 H), 3.43-3.67 (m, 2.5 H), 3.67-3.85 (m, 2 H), 5.54 (br. s., 1 H), 6.53 (br. s., 1 H), 7.28-7.45 (m, 4 H), 7.52-7.67 (m, 1 H), 7.79 (s, 1 H), 8.77 (br. s., 1 H). MS m/z 471 (M + H)+ 235

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4′-(pyridin-4-yl)-[1,1′- biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.68-0.81 (m, 2 H), 0.95 (dt, J = 7.1, 3.6 Hz, 2 H), 1.47-1.58 (m, 1 H), 1.77- 1.93 (m, 4 H), 1.96-2.11 (m, 1 H), 2.37- 2.52 (m, 1 H), 2.58 (d, J = 7.6 Hz, 1 H), 3.06 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.23- 3.41 (m, 1 H), 3.49-3.74 (m, 2.5 H), 3.78- 3.89 (m, 2 H), 7.58 (d, J = 5.9 Hz, 2 H), 7.67-7.76 (m, 2 H), 7.76-7.89 (m, 6 H), 8.71 (d, J = 5.5 Hz, 2 H). MS m/z 491 (M + H)+ 236

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-fluoro-4-(1H-indol-6- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.57-0.74 (m, 4 H), 1.38-1.57 (m, 1 H), 1.57-1.68 (m, 3 H), 1.71-1.84 (m, 2 H), 1.84-1.97 (m, 1 H), 2.22-2.36 (m, 1 H), 2.92 (dd, J = 11.8, 6.8 Hz, 0.5 H), 3.11- 3.24 (m, 1 H), 3.24-3.32 (m, 1 H), 3.46- 3.66 (m, 1.5 H), 3.78 (t, J = 6.5 Hz, 2 H), 6.50 (br. s., 1 H), 7.26 (d, J = 8.1 Hz, 1 H), 7.46 (br. s., 1 H), 7.59-7.80 (m, 5 H), 11.28 (br. s., 1 H). MS m/z 471 (M + H)+ 237

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-fluoro-4-(1H-indazol-4- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.61-0.70 (m, 4 H), 1.41-1.60 (m, 1 H), 1.64 (br. s., 3 H), 1.80-1.85 (m, 2 H), 1.92 (d, J = 6.3 Hz, 1 H), 2.26-2.38 (m, 0.5 H), 2.38-2.48 (m, 0.5 H), 2.92 (dd, J = 11.8, 6.7 Hz, 0.5 H), 3.11-3.31 (m, 2 H), 3.46-3.66 (m, 1.5 H), 3.80 (t, J = 6.7 Hz, 2 H), 7.27 (d, J = 6.7 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 1 H), 7.61-7.75 (m, 3 H), 7.75- 7.85 (m, 2 H), 8.00 (br. s., 1 H), 13.29 (br. s., 1 H). MS m/z 472 (M + H)+ 238

(R)-5-(4-(1H-indol-5-yl)-3-methylphenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.68 (br. s., 4 H), 1.35-1.56 (m, 1 H), 1.56-1.69 (m, 3 H), 1.78 (d, J = 3.8 Hz, 2 H), 1.89 (dd, J = 12.4, 6.1 Hz, 1 H), 2.27- 2.35 (m, 3 H), 2.43 (d, J = 13.6 Hz, 1 H), 2.94 (dd, J = 11.8, 6.7 Hz, 0.5 H), 3.10- 3.23 (m, 1 H), 3.23-3.33 (m, 1 H), 3.45- 3.63 (m, 1.5 H), 3.77 (t, J = 7.4 Hz, 2 H), 6.48 (br. s., 1 H), 7.11 (d, J = 8.2 Hz, 1 H), 7.34-7.44 (m, 2 H), 7.44-7.66 (m, 4 H), 11.20 (br. s., 1 H). MS m/z 467 (M + H)+ 239

(R)-5-(4-(1H-indol-6-yl)-3-methylphenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.61-0.74 (m, 4 H), 1.39-1.53 (m, 0.5 H), 1.54-1.68 (m, 3.5 H), 1.73-1.95 (m, 3 H), 2-27-2.48 (m, 1 H) 2.35 (s, 3 H), 2.88-3.00 (m, 0.5 H), 3.11-3.23 (m, 1 H), 3.25-3.42 (m, 1 H), 3.46-3.63 (m, 1.5 H), 3.77 (t, J = 7.3 Hz, 2 H), 6.49 (br s, 1 H), 7.02 (d, J = 8.0 Hz, 1 H), 7.35-7.45 (m, 3 H), 755-7.68 (m, 3 H), 11.19 (br s, 1H). MS m/z 467 (M + H)+ 240

(R)-5-(4-(benzofuran-5-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.71 (m, 4 H), 1.35-1.68 (m, 4 H), 1.72-1.92 (m, 3 H), 2.21-2.33 (m, 1 H), 2.87 (dd, J = 11.7, 7.0 Hz, 0.5 H), 3.08- 3.31 (m, 2 H), 3.41-3.53 (m, 1.5 H), 3.53- 3.63 (m, 2 H), 7.05 (d, J = 1.8 Hz, 1 H), 7.68-7.88 (m, 5 H), 8.04-8.14 (m, 2 H). MS m/z 472 (M + H)+ 241

(R)-5-(4-(benzo[b]thiophen-5-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.72 (m, 4 H), 1.35-1.70 (m, 4 H), 1.70-1.95 (m, 3 H), 2.29 (d, J = 7.0 Hz, 0.5 H), 2.38 (br. s., 0.5 H), 2.87 (dd, J = 11.7, 6.9 Hz, 0.5 H), 3.07-3.32 (m, 2 H), 3.47 (t, J = 6.9 Hz, 1 H), 3.53-3.64 (m, 2.5 H), 7.55 (d, J = 5.4 Hz, 1 H), 7.73- 7.93 (m, 5 H), 8.15 (d, J = 8.4 Hz, 1 H), 8.35 (s, 1 H). MS m/z 488 (M + H)+ 242

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(2- methylbenzofuran-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.74 (m, 4 H), 1.31-1.68 (m, 4 H), 1.79-1.94 (m, 3 H), 2.19-2.34 (m, 1 H), 2.48 (s, 3 H), 2.86 (dd, J = 11.8, 7.1 Hz, 0.5 H), 3.07-3.32 (m, 2 H), 3.43-3.51 (m, 1 H), 3.51-3.63 (m, 2.5 H), 6.66 (s, 1 H), 7.56-7.86 (m, 5 H), 7.96 (s, 1 H). MS m/z 486 (M + H)+ 243

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.72 (m, 4 H), 1.33-1.69 (m, 4 H), 1.69-1.94 (m, 3 H), 2.20-2.33 (m, 0.5 H), 2.33-2.47 (m, 0.5 H), 2.60 (s, 3 H), 2.86 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06- 3.32 (m, 2 H), 3.41-3.51 (m, 1 H), 3.51- 3.64 (m, 2.5 H), 7.21 (s, 1 H), 7.65-7.90 (m, 4 H), 8.00 (d, J = 8.4 Hz, 1 H), 8.17 (s, 1 H). MS m/z 502 (M + H)+ 244

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-2-fluorophenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.57-0.75 (m, 4 H), 1.32-1.52 (m, 1 H), 1.52-1.69 (m, 3 H), 1.69-1.95 (m, 3 H), 2.21 (s, 3 H), 2.24-2.38 (m, 1 H), 2.41 (s, 3 H), 2.86 (dd, J = 11.7, 7.0 Hz, 0.5 H), 3.05-3.32 (m, 2 H), 3.42-3.51 (m, 1 H), 3.51-3.64 (m, 2.5 H), 7.50-7.60 (m, 1 H), 7.62-7.90 (m, 4 H), 7.94 (s, 1 H). MS m/z 500 (M + H)+ 245

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3- dimethylbenzo[b]thiophen-5-yl)-2- fluorophenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.31-0.46 (m, 4 H), 1.07-1.43 (m, 4 H), 1.45-1.69 (m, 3 H), 1.94-2.09 (m, 1 H), 2.12 (s, 3 H), 2.25 (s, 3 H), 2.62 (dd, J = 11.8, 6.9 Hz, 0.5 H), 2.82-3.07 (m, 2 H), 3.12-3.27 (m, 1.5 H), 3.28-3.39 (m, 2 H), 7.42-7.76 (m, 5 H), 7.82 (s, 1 H). MS m/z 516 (M + H)+ 246

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.73 (m, 4 H), 1.49-1.68 (m, 4 H), 1.68-1.95 (m, 3 H), 2.28 (br. s., 0.5 H), 2.37 (br. s., 0.5 H), 2.87 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07-3.29 (m, 2 H), 3.43- 3.52 (m, 1 H), 3.58 (br. s., 2.5 H), 6.53 (br. s., 1 H), 7.42 (t, J = 2.5 Hz, 1 H), 7.46- 7.59 (m, 2 H), 7.61-7.83 (m, 3 H), 8.01 (s, 1 H), 11.27 (br. s., 1 H). MS m/z 471 (M + H)+ 247

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(1H-indol-6- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.57-0.71 (m, 4 H), 1.33-1.60 (m, 2 H), 1.60-1.68 (m, 2 H), 1.79-1.94 (m, 3 H), 2.22-2.35 (m, 0.5 H), 2.35-2.48 (m, 0.5 H), 2.88 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07- 3.32 (m, 2 H), 3.39-3.52 (m, 1.5 H), 3.58 (t, J = 8.3 Hz, 2 H), 6.50 (br. s., 1 H), 7.40-7.49 (m, 2 H), 7.63-7.84 (m, 5 H), 11.30 (br. s., 1 H). MS m/z 471 (M + H)+ 248

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(quinolin-6- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.72 (m, 4 H), 1.37-1.68 (m, 4 H), 1.71-1.93 (m, 3 H), 2.21-2.48 (m, 1 H), 2.82-2.92 (m, 0.5 H), 3.06-3.32 (m, 2 H), 3.43-3.53 (m, 1 H), 3.53-3.66 (m, 2.5 H), 7.61 (dd, J = 8.2, 4.1 Hz, 1 H), 7.82 (dt, J = 11.7, 7.7 Hz, 1 H), 7.88-8.04 (m, 2 H), 8.15 (d, J = 8.7 Hz, 1 H), 8.23 (d, J = 8.7 Hz, 1 H), 8.40-8.54 (m, 2 H), 8.87-9.06 (m, 1 H). MS m/z 483 (M + H)+ 249

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(quinolin-7- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.70 (m, 4 H), 1.36-1.70 (m, 4 H), 1.70-1.96 (m, 3 H), 2.22-2.36 (m, 1 H), 2.88 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06- 3.32 (m, 2 H), 3.47 (t, J = 7.1 Hz, 1 H), 3.52-3.66 (m, 2.5 H), 7.59 (dd, J = 8.2, 4.3 Hz, 1 H), 7.81 (dt, J = 11.9, 7.7 Hz, 1 H), 7.89-8.18 (m, 4 H), 8.39-8.51 (m, 2 H), 8.89-9.06 (m, 1 H). MS m/z 483 (M + H)+ 250

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(quinolin-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.67 (d, J = 6.0 Hz, 4 H), 1.45 (dd, J = 12.5, 7.3 Hz, 1 H), 1.57-1.71 (m, 3 H), 1.74- 1.88 (m, 2 H), 1.88-2.01 (m, 1 H), 2.23- 2.42 (m, 1 H), 2.88 (dd, J = 11.6, 6.9 Hz, 0.5 H), 3.10-3.31 (m, 2 H), 3.51 (t, J = 6.5 Hz, 1 H), 3.56-3.70 (m, 2.5 H), 7.46- 7.73 (m, 4 H), 7.76-7.96 (m, 2 H), 8.14 (d, J = 8.4 Hz, 1 H), 8.27 (dd, J = 15.9, 8.6 Hz, 1 H), 8.98 (d, J = 3.4 Hz, 1 H). MS m/z 483 (M + H)+ 251

(R)-5-(4-(benzo[d]oxazol-2-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.75 (m, 4 H), 1.32-1.71 (m, 4 H), 1.71-1.94 (m, 3 H), 2.18-2.32 (m, 1 H), 2.85 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.05- 3.30 (m, 2 H), 3.41-3.53 (m, 1 H), 3.53- 3.66 (m, 2.5 H), 7.42-7.57 (m, 2 H), 7.79- 8.00 (m, 3 H), 8.11-8.29 (m, 2 H). MS m/z 473 (M + H)+ 252

(R)-5-(4-(benzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.73 (m, 4 H), 1.32-1.53 (m, 1 H), 1.58 (dd, J = 5.7, 2.3 Hz, 1 H), 1.63-1.70 (m, 2 H), 1.77 (br. s., 1 H), 1.81-1.95 (m, 2 H), 2.21-2.33 (m, 1 H), 2.86 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.06-3.31 (m, 2 H), 3.42-3.53 (m, 1 H), 3.53-3.66 (m, 2.5 H), 7.48-7.66 (m, 2 H), 7.88 (dt, J = 12.7, 7.7 Hz, 1 H), 8.06-8.18 (m, 3 H), 8.23 (d, J = 7.8 Hz, 1 H). MS m/z 489 (M + H)+ 253

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(1H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.72 (m, 4 H), 1.35-1.69 (m, 4 H), 1.69-1.95 (m, 3 H), 2.17-2.33 (m, 0.5 H), 2.33-2.46 (m, 0.5 H), 2.87 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.05-3.31 (m, 2 H), 3.43-3.52 (m, 1 H), 3.52-3.67 (m, 2.5 H), 7.54-7.91 (m, 5 H), 8.23 (s, 1 H), 8.18 (s, 1 H), 13.23 (br. s., 1 H). MS m/z 472 (M + H)+ 254

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-fluorophenyl)benzofuran-2- carbonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.72 (m, 4 H), 1.47-1.69 (m, 4 H), 1.69-1.94 (m, 3 H), 2.20-2.33 (m, 0.5 H), 2.40 (d, J = 7.0 Hz, 0.5 H), 2.86 (dd, J = 11.8, 7.0 Hz, 0.5 H), 3.06-3.31 (m, 2 H), 3.43-3.52 (m, 1 H), 3.52-3.64 (m, 2.5 H), 7.73-7.82 (m, 2 H), 7.83-7.94 (m, 2 H), 8.05 (d, J = 9.1 Hz, 1 H), 8.20 (s, 1 H), 8.28 (s, 1 H). MS m/z 497 (M + H)+ 255

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)benzofuran-2- carbonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.42 (d, J = 5.2 Hz, 4 H), 1.07-1.28 (m, 1 H), 1.38 (br. s., 3 H), 1.45-1.71 (m, 3 H), 1.91-2.11 (m, 1 H), 2.15 (br. s., 3 H), 2.62 (dd, J = 11.3, 6.7 Hz, 0.5 H), 2.80- 3.06 (m, 2 H), 3.16-3.36 (m, 3.5 H), 7.36 (dd, J = 13.0, 8.0 Hz, 1 H), 7.47 (br. s., 1 H), 7.55 (br. s., 1 H), 7.63 (d, J = 8.7 Hz, 1 H), 7.75 (d, J = 8.7 Hz, 1 H), 7.95 (d, J = 7.1 Hz, 2 H). MS m/z 493 (M + H)+ 256

(R)-5-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)benzofuran-2- carbonitrile ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.71 (m, 4 H), 1.37-1.67 (m, 4 H), 1.69-1.94 (m, 3 H), 2.20-2.33 (m, 0.5 H), 2.38 (d, J = 6.9 Hz, 0.5 H), 2.90 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07-3.31 (m, 2 H), 3.40-3.62 (m, 1.5 H), 3.77 (t, J = 6.3 Hz, 2 H), 7.79-7.95 (m, 5 H), 7.95-8.04 (m, 1 H), 8.18 (s, 1 H), 8.21 (s, 1 H). MS m/z 479 (M + H)+ 257

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(quinolin-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.83 (m, 2 H), 0.85-1.07 (m, 2 H), 1.39-1.60 (m, 1 H), 1.60-1.77 (m, 1 H), 1.80-2.08 (m, 5 H), 2.38-2.53 (m, 1 H), 2.92-3.10 (m, 0.5 H), 3.18-3.41 (m, 1 H), 3.50-3.83 (m, 4.5 H), 7.54- 7.88 (m, 5 H), 7.93 (d, J = 7.8 Hz, 1 H), 8.18 (d, J = 8.5 Hz, 1 H), 8.33-8.50 (m, 1 H), 9.20 (d, J = 2.3 Hz, 1 H). MS m/z 483 (M + H)+ 258

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(quinazolin-7- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.50-0.71 (m, 2 H), 0.72-0.95 (m, 2 H), 1.34-1.49 (m, 1 H), 1.51-1.68 (m, 1 H), 1.68-1.79 (m, 2 H), 1.79-1.88 (m, 2 H), 1.89-2.02 (m, 1 H), 2.29-2.44 (m, 0.5 H), 2.44-2.61 (m, 0.5 H), 2.90 (dd, J = 12.0, 7.3 Hz, 0.5 H), 3.10-3.31 (m, 1 H), 3.40-3.58 (m, 2.5 H), 3.59-3.76 (m, 2 H), 7.54 (dd, J = 10.9, 5.9 Hz, 1 H), 7.59- 7.71 (m, 2 H), 7.87 (d, J = 8.4 Hz, 1 H), 8.01 (d, J = 8.4 Hz, 1 H), 8.22 (s, 1 H), 9.32 (s, 1 H), 9.40 (s, 1 H). MS m/z 484 (M + H)+ 259

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(6- fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.55-0.70 (m, 2 H), 0.75-0.94 (m, 2 H), 1.34-1.48 (m, 1.5 H), 1.52-1.63 (m, 0.5 H), 1.69-1.76 (m, 2 H), 1.78- 1.87 (m, 2 H), 1.87-2.01 (m, 1 H), 2.36 (dt, J = 14.5, 7.3 Hz, 1 H), 2.90 (dd, J = 12.0, 7.3 Hz, 0.5 H), 3.09-3.30 (m, 1 H), 3.37-3.58 (m, 2.5 H), 3.58-3.72 (m, 2 H), 7.26 (td, J = 8.7, 2.0 Hz, 1 H), 7.38- 7.53 (m, 2 H), 7.58 (d, J = 3.8 Hz, 2 H), 7.68 (d, J = 8.2 Hz, 1 H), 7.79-7.90 (m, 2 H), 8.01 (s, 1 H). MS m/z 500 (M + H)+ 260

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(8- fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.40-0.56 (m, 2 H), 0.70 (br. s., 2 H), 1.18-1.33 (m, 1.5 H), 1.36-1.51 (m, 0.5 H), 1.55-1.63 (m, 2 H), 1.64-1.72 (m, 2 H), 1.73-1.87 (m, 1 H), 2.20-2.38 (m, 1 H), 2.77 (dd, J = 11.8, 7.3 Hz, 0.5 H), 2.93-3.17 (m, 1 H), 3.22-3.44 (m, 2.5 H), 3.44-3.62 (m, 2 H), 6.93-7.10 (m, 1 H), 7.17-7.31 (m, 1 H), 7.32-7.42 (m, 1 H), 7.46 (d, J = 6.7 Hz, 3 H), 7.57 (d, J = 8.7 Hz, 1 H), 7.76 (d, J = 8.5 Hz, 1 H), 8.13 (s, 1 H). MS m/z 500 (M + H)+ 261

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(1H-indol-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.54-0.71 (m, 2 H), 0.74-0.95 (m, 2 H), 1.32-1.49 (m, 1.5 H), 1.54-1.66 (m, 1 H), 1.68-1.76 (m, 2 H), 1.77-1.85 (m, 2 H), 1.86-2.01 (m, 0.5 H), 2.28- 2.59 (m, 1 H), 2.94 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.09-3.31 (m, 1 H), 3.42-3.59 (m, 2.5 H), 3.59-3.72 (m, 2 H), 7.06- 7.27 (m, 2 H), 7.40 (d, J = 2.9 Hz, 1 H), 7.37 (d, J = 2.2 Hz, 1 H), 7.42-7.58 (m, 3 H), 7.86 (d, J = 7.6 Hz, 1 H), 8.93 (d, J = 6.6 Hz, 1 H). MS m/z 471 (M + H)+ 262

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.71 (dd, J = 4.7, 3.0 Hz, 2 H), 0.90- 1.01 (m, 2 H), 1.43-1.56 (m, 1.5 H), 1.59- 1.74 (m, 0.5 H), 1.76-1.83 (m, 2 H), 1.84-1.89 (m, 2 H), 1.89-2.08 (m, 1 H), 2.43 (s, 3 H), 2.45-2.60 (m, 1 H), 3.00 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.15-3.39 (m, 1 H), 3.41-3.73 (m, 4.5 H), 4.14 (s, 3 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.55-7.63 (m, 2 H), 7.65-7.73 (m, 1 H), 7.98 (s, 1 H), 8.06 (s, 1 H). MS m/z 482 (M + H)+ 263

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-methyl-4-(2-methyl-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.36-0.52 (m, 2 H), 0.59-0.71 (m, 2 H), 0.98-1.11 (m, 2 H), 1.42-1.57 (m, 2 H), 1.57-1.76 (m, 3 H), 2.15 (s, 3 H), 2.22 (s, 3 H), 2.50 (dd, J = 7.6, 6.4 Hz, 1 H), 3.27-3.37 (m, 1 H), 3.38-3.51 (m, 1 H), 3.51-3.66 (m, 2 H), 3.66-3.78 (m, 1 H), 3.96 (t, J = 8.2 Hz, 1 H), 6.03 (s, 1 H), 7.04-7.17 (m, 3 H), 7.26-7.42 (m, 2 H), 7.51 (s, 1 H), 8.19 (br. s., 1 H). MS m/z 467 (M + H)+ 264

5-(2-chloro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.42-0.52 (m, 2 H), 0.70 (d, J = 3.2 Hz, 2 H), 1.34-1.44 (m, 2 H), 1.51-1.63 (m, 2 H), 2.30-2.44 (m, 1 H), 3.19 (br. s., 1 H), 3.46 (t, J = 6.9 Hz, 2 H), 3.55 (br. s., 1 H), 3.79 (br. s., 1 H), 3.86 (s, 3 H), 4.14 (br. s., 1 H), 5.66 (br. s., 1 H), 7.47-7.58 (m, 2 H), 7.59-7.70 (m, 2 H), 7.80 (s, 1 H), 7.90 (s, 1 H), 7.99 (s, 1 H). MS m/z 504 (M + H)+ 265

(R)-5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.40 (br. s., 2 H), 0.57-0.83 (m, 2 H), 1.10 (br. s., 4 H), 1.43 (br. s., 1 H), 1.61 (br. s., 2 H), 1.79 (br. s., 3 H), 2.27 (br. s., 1 H), 2.39 (br. s., 3 H), 2.99 (br. s., 1 H), 3.18 (br. s., 2 H), 3.48 (br. s., 3 H), 4.10 (br. s., 3 H), 7.57 (br. s., 1 H), 7.79 (br. s., 4 H), 8.13 (br. s., 2 H). MS m/z 496 (M + H)+ 266

(R)-5-(4-(6-fluoronaphthalen-2-yl)-2- methylphenyl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.27 (br. s., 2 H), 0.59 (t, J = 10.7 Hz, 2 H), 0.97 (s, 3 H), 1.30 (br. s., 1 H), 1.43- 1.53 (m, 2 H), 1.67 (d, J = 4.0 Hz, 3 H), 2.13 (br. s., 1 H), 2.28 (s, 3 H), 2.80 (d, J = 19.2 Hz, 1 H), 2.98-3.18 (m, 1.5 H), 3.24-3.30 (m, 1 H), 3.35 (br. s., 2.5 H), 7.31-7.41 (m, 1 H), 7.43-7.53 (m, 1 H), 7.60-7.72 (m, 2 H), 7.76 (s, 1 H), 7.85 (d, J = 8.7 Hz, 1 H), 7.92 (d, J = 8.7 Hz, 1 H), 8.00 (dd, J = 9.0, 5.8 Hz, 1 H), 8.26 (s, 1 H). MS m/z 510 (M + H)+ 267

(R)-5-(3-methyl-4′-(1-methyl-1H-pyrazol- 4-yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 522 (M + H)+ 268

2-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3- fluorophenyl)benzo[d]thiazole-6- carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62 (dd, J = 7.4, 3.2 Hz, 2 H), 0.77- 0.88 (m, 2 H), 1.22 (td, J = 7.9, 4.1 Hz, 1 H), 1.70-1.80 (m, 2 H), 1.80-1.90 (m, 2 H), 2.69-2.85 (m, 1 H), 3.39-3.50 (m, 1 H), 3.63-3.76 (m, 1 H), 3.81-3.95 (m, 3 H), 4.19 (t, J = 8.2 Hz, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 7.73 (d, J = 8.4 Hz, 1 H), 7.91- 8.04 (m, 2 H), 8.12 (d, J = 8.5 Hz, 1 H), 8.23 (s, 1 H). MS m/z 500 (M + H)+ 269

6-(3-methyl-4-(6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.44 (br. s., 2 H), 0.98 (br. s., 2 H), 1.20 (br. s., 3 H), 1.76 (br. s., 1 H), 1.82 (br. s., 2 H), 1.89 (br. s., 2 H), 2.47 (br. s., 3 H), 2.77 (br. s., 1 H), 3.49 (br. s., 1 H), 3.70-3.82 (m, 2 H), 4.14 (br. s., 2 H), 7.50 (d, J = 7.3 Hz, 1 H), 7.71 (d, J = 6.3 Hz, 3 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.96- 8.08 (m, 2 H), 8.13 (br. s., 1 H), 8.29 (br. s., 1 H). MS m/z 503 (M + H)+ 270

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6- methylbenzo[d]thiazol-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.46 (br. s., 2 H), 0.66 (br. s., 2 H), 1.06 (br. s., 1 H), 1.59 (br. s., 2 H), 1.67 (br. s., 2 H), 2.30 (br. s., 3 H), 2.59 (br. s., 1 H), 3.34 (br. s., 1 H), 3.46-3.62 (m, 1 H), 3.71 (br. s., 3 H), 4.01 (br. s., 1 H), 7.13 (d, J = 7.7 Hz, 1 H), 7.44 (br. s., 1 H), 7.52 (br. s., 1 H), 7.66-7.95 (m, 3 H). MS m/z 489 (M + H)+ 271

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6- fluorobenzo[d]thiazol-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.71 (br. s., 2 H), 0.91 (br. s., 2 H), 1.31 (br. s., 1 H), 1.82 (br. s., 2 H), 1.92 (br. s., 2 H), 2.84 (br. s., 1 H), 3.57 (br. s., 1 H), 3.81 (d, J = 5.6 Hz, 1 H), 3.97 (d, J = 7.7 Hz, 3 H), 4.26 (br. s., 1 H), 7.29 (br. s., 1 H), 7.56-7.79 (m, 2 H), 7.86-8.20 (m, 3 H). MS m/z 493 (M + H)+ 272

6-(4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)-2- naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.81 (br. s., 2 H), 1.12 (br. s., 2 H), 1.71 (br. s., 2 H), 1.79 (br. s., 2 H), 2.54- 2.75 (m, 1 H), 3.47 (br. s., 1 H), 3.68 (br. s., 2 H), 3.80-4.17 (m, 2 H), 4.35 (br. s., 1 H), 7.39 (d, J = 7.7 Hz, 1 H), 7.54-7.66 (m, 3 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.92 (dd, J = 8.1, 3.0 Hz, 2 H), 8.04 (s, 1 H), 8.20 (s, 1 H). MS m/z 505 (M + H)+ 273

6-(4-(6-((1-(1- fluorocyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)-2- naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.97-1.15 (m, 2 H), 1.15-1.28 (m, 2 H), 1.68-1.76 (m, 2 H), 1.76-1.86 (m, H), 2.67-2.85 (m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1 H), 3.70 (t, J = 6.7 Hz, 2 H), 3.87-4.03 (m, 2 H), 4.32 (br. s., 1 H), 7.40 (d, J = 7.8 Hz, 1 H), 7.54-7.67 (m, 3 H), 7.81 (d, J = 8.5 Hz, 1 H), 7.93 (dd, J = 8.5, 3.9 Hz, 2 H), 8.05 (s, 1 H), 8.20 (s, 1 H). MS m/z 507 (M + H)+ 274

5-(4-(6-chlorobenzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.2, 3.1 Hz, 2 H), 0.81 (br. s., 2 H), 1.21 (td, J = 7.8, 3.8 Hz, 1 H), 1.68-1.79 (m, 2 H), 1.79-1.89 (m, 2 H), 2.65-2.86 (m, 1 H), 3.39-3.55 (m, 1 H), 3.71 (d, J = 6.6 Hz, 1 H), 3.76-3.98 (m, 3 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.37-7.49 (m, 1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.86 (s, 1 H), 7.88-8.04 (m, 3 H). MS m/z 509 (M + H)+ 275

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-fluoroquinolin-2- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.76 (m, 2 H), 0.85-0.98 (m, 2 H), 1.20-1.40 (m, 1 H), 1.79-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.74-2.93 (m, 1 H), 3.61 (dd, J = 9.6, 5.5 Hz, 1 H), 3.88- 4.04 (m, 3 H), 4.04-4.15 (m, 1 H), 4.23 (t, J = 8.2 Hz, 1 H), 7.43-7.62 (m, 2 H), 7.76 (d, J = 8.2 Hz, 2 H), 7.97 (d, J = 8.5 Hz, 1 H), 8.14-8.30 (m, 2 H), 8.34 (d, J = 8.2 Hz, 2 H). MS m/z 469 (M + H)+ 276

6-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)quinoline-2-carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62 (dd, J = 7.1, 4.0 Hz, 2 H), 0.82 (t, J = 3.6 Hz, 2 H), 1.14-1.30 (m, 1 H), 1.70- 1.77 (m, 2 H), 1.77-1.87 (m, 2 H), 2.70- 2.87 (m, 1 H), 3.51 (dd, J = 9.6, 5.5 Hz, 1 H), 3.81-3.96 (m, 3 H), 3.96-4.10 (m, 1 H), 4.18 (t, J = 8.2 Hz, 1 H), 7.62-7.74 (m, 3 H), 7.82 (d, J = 8.1 Hz, 2 H), 8.00-8.12 (m, 2 H), 8.15-8.26 (m, 1 H), 8.31 (d, J = 8.5 Hz, 1 H). MS m/z 476 (M + H)+ 277

2-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)quinoline-6-carbonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.51-0.71 (m, 2 H), 0.82 (br. s., 2 H), 1.14-1.27 (m, 1 H), 1.64 (br. s., 2 H), 1.73 (br. s., 2 H), 2.75 (br. s., 1 H), 3.51 (br. s., 1 H), 3.75-3.95 (m, 3 H), 3.95- 4.08 (m, 1 H), 4.08-4.25 (m, 1 H), 7.71 (d, J = 7.8 Hz, 2 H), 7.83 (d, J = 8.5 Hz, 1 H), 7.99 (d, J = 8.5 Hz, 1 H), 8.09-8.24 (m, 2 H), 8.24-8.44 (m, 3 H). MS m/z 509 (M + H)+ 278

(R)-5-(4-(benzofuran-5-yl)-2- methylphenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.33-0.46 (m, 4 H), 1.10-1.28 (m, 1 H), 1.28-1.41 (m, 3 H), 1.44-1.69 (m, 3 H), 1.91-2.10 (m, 1 H), 2.14 (s, 3 H), 2.62 (dd, J = 11.7, 6.6 Hz, 0.5 H), 2.82-3.05 (m, 2 H), 3.15-3.37 (m, 3.5 H), 6.80 (s, 1 H), 7.32 (dd, J = 13.0, 7.9 Hz, 1 H), 7.40- 7.50 (m, 3 H), 7.52 (br. s., 1 H), 7.79 (s, 1 H), 7.82 (d, J = 1.9 Hz, 1 H). MS m/z 468 (M + H)+ 279

(R)-5-(4-(benzo[b]thiophen-5-yl)-2- methylphenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.71 (m, 4 H), 1.39-1.65 (m, 4 H), 1.76-1.82 (m, 2 H), 1.82-1.94 (m, 1 H), 2.23 (d, J = 6.6 Hz, 1 H), 2.39 (s, 3 H), 2.81-2.92 (m, 0.5 H), 3.04-3.30 (m, 2 H), 3.47 (d, J = 7.1 Hz, 2.5 H), 3.55-3.66 (m, 1 H), 7.51-7.63 (m, 2 H), 7.69-7.79 (m, 2 H), 7.83 (t, J = 5.3 Hz, 2 H), 8.13 (d, J = 8.4 Hz, 1 H), 8.28 (s, 1 H). MS m/z 484 (M + H)+ 280

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-methyl-4-(2- methylbenzofuran-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.73 (m, 4 H), 1.43-1.65 (m, 4 H), 1.65-1.93 (m, 3 H), 2.13-2.33 (m, 1 H), 2.37 (s, 3 H), 2.79-2.92 (m, 0.5 H), 3.04- 3.29 (m, 2 H), 3.37-3.62 (m, 3.5 H), 6.65 (s, 1 H), 7.48-7.57 (m, 1 H), 7.57- 7.61 (m, 2 H), 7.71-7.78 (m, 1 H), 7.89 (s, 1 H). MS m/z 482 (M + H)+ 281

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-methyl-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 5.8 Hz, 4 H), 1.34-1.49 (m, 1 H), 1.49-1.66 (m, 3 H), 1.68-1.84 (m, 3 H), 2.24 (br. s., 1 H), 2.38 (s, 3 H), 2.60 (s, 3 H), 2.85 (d, J = 11.7 Hz, 0.5 H), 3.04- 3.29 (m, 2 H), 3.36-3.53 (m, 2.5 H), 3.53- 3.62 (m, 1 H), 7.22 (s, 1 H), 7.57 (dd, J = 13.4, 8.0 Hz, 1 H), 7.62-7.75 (m, 2 H), 7.78 (br. s., 1 H), 7.98 (d, J = 8.4 Hz, 1 H), 8.10 (s, 1 H). MS m/z 498 (M + H)+ 282

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-2-methylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.46 (d, J = 5.5 Hz, 4 H), 1.14-1.35 (m, 1 H), 1.41 (br. s., 3 H), 1.49-1.64 (m, 3 H), 1.64-1.75 (m, 1 H), 2.02 (s, 3 H), 2.18 (s, 3 H), 2.22 (s, 3 H), 2.60-2.71 (m, 0.5 H), 2.86-3.00 (m, 1 H), 3.07 (br. s., 1 H), 3.15-3.42 (m, 3.5 H), 7.29-7.44 (m, 3 H), 7.48 (br. s., 1 H), 7.57 (br. s., 1 H), 7.65 (s, 1 H). MS m/z 496 (M + H)+ 283

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3- dimethylbenzo[b]thiophen-5-yl)-2- methylphenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.50-0.78 (m, 4 H), 1.32-1.48 (m, 1 H), 1.48-1.64 (m, 3 H), 1.69-1.83 (m, 2 H), 1.83-1.94 (m, 1 H), 2.14-2.34 (m, 1 H), 2.38 (d, J = 5.4 Hz, 6 H), 2.81-2.93 (m, 0.5 H), 3.06-3.23 (m, 1 H), 3.28 (d, J = 4.9 Hz, 1 H), 3.41-3.62 (m, 3.5 H), 7.57 (dd, J = 13.8, 7.9 Hz, 1 H), 7.64-7.71 (m, 1 H), 7.74 (br. s., 1 H), 7.81-7.87 (m, 1 H), 7.93-8.03 (m, 2 H). MS m/z 512 (M + H)+ 284

(R)-5-(4-(1H-indol-5-yl)-2-methylphenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.57-0.71 (m, 4 H), 1.44 (d, J = 7.4 Hz, 1 H), 1.60 (br. s., 3 H), 1.78 (d, J = 3.8 Hz, 3 H), 1.87 (d, J = 6.0 Hz, 1 H), 2.25 (br. s., 1 H), 2.37 (s, 3 H), 2.88 (br. s., 0.5 H), 3.05- 3.20 (m, 1 H), 3.26 (d, J = 7.0 Hz, 1 H), 3.43-3.53 (m, 2.5 H), 6.44-6.59 (m, 1 H), 7.40 (br. s., 1 H), 7.44-7.57 (m, 3 H), 7.64 (br. s., 1 H), 7.72 (br. s., 1 H), 7.93 (s, 1 H), 11.18 (br. s., 1 H). MS m/z 467 (M + H)+ 286

(R)-5-(4-(1H-indazol-5-yl)-2- methylphenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.32-0.51 (m, 4 H), 1.15 (d, J = 12.4 Hz, 1 H), 1.38 (br. s., 3 H), 1.56 (d, J = 3.8 Hz, 2 H), 1.65 (br. s., 1 H), 2.02 (br. s., 1 H), 2.15 (s, 3 H), 2.64 (dd, J = 11.9, 6.7 Hz, 0.5 H), 2.87-3.10 (m, 3.5 H), 3.23 (br. s., 1 H), 3.25 (br. s., 1 H), 7.33 (dd, J = 13.1, 8.0 Hz, 1 H), 7.39-7.50 (m, 2 H), 7.53 (d, J = 8.8 Hz, 2 H), 7.92 (d, J = 4.0 Hz, 2 H), 12.3 (br. s., 1 H). MS m/z 468 (M + H)+ 287

5-(4-(benzofuran-5-yl)-2-methylphenyl)-6- ((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.68 (m, 4 H), 1.37 (t, J = 6.1 Hz, 1 H), 1.55-1.65 (m, 2 H), 1.72-1.83 (m, 2 H), 2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J = 9.6, 5.4 Hz, 1 H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.04 (d, J = 1.9 Hz, 1 H), 7.56 (d, J = 8.0 Hz, 1 H), 7.66-7.74 (m, 3 H), 7.77 (s, 1 H), 8.03 (s, 1 H), 8.06 (d, J = 2.1 Hz, 1 H). MS m/z 454 (M + H)+ 288

5-(4-(benzo[b]thiophen-5-yl)-2- methylphenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.70 (m, 4 H), 1.29-1.44 (m, 1 H), 1.53-1.66 (m, 2 H), 1.73-1.84 (m, 2 H), 2.37 (s, 3 H), 2.55-2.70 (m, 1 H), 3.33- 3.44 (m, 1 H), 3.64-3.83 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 7.50-7.63 (m, 2 H), 7.70-7.80 (m, 2 H), 7.80-7.88 (m, 2 H), 8.13 (d, J = 8.5 Hz, 1 H), 8.28 (s, 1 H). MS m/z 470 (M + H)+ 289

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-methyl-4-(2- methylbenzofuran-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.48-0.71 (m, 4 H), 1.26-1.46 (m, 1 H), 1.54-1.65 (m, 2 H), 1.78 (d, J = 3.7 Hz, 2 H), 2.36 (s, 3 H), 2.48 (s, 3 H), 2.54-2.68 (m, 1 H), 3.38 (br. s., 1 H), 3.61-3.83 (m, 4 H), 4.17 (t, J = 8.3 Hz, 1 H), 6.65 (s, 1 H), 7.51-7.63 (m, 3 H), 7.66 (s, 1 H), 7.75 (s, 1 H), 7.89 (s, 1 H). MS m/z 468 (M + H)+ 290

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2,3- dimethylbenzo[b]thiophen-5-yl)-2- methylphenyl)-4,6-diazaspiro[2.4]hept-4- en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.71 (m, 4 H), 1.37 (t, J = 6.0 Hz, 1 H), 1.55-1.65 (m, 2 H), 1.74-1.84 (m, 2 H), 2.37 (s, 6 H), 2.47 9s, 3 H), 2.56- 2.69 (m, 1 H), 3.39 (d, J = 5.5 Hz, 1 H), 3.70 (d, J = 7.4 Hz, 3 H), 3.79 (br. s., 1 H), 4.17 (t, J = 8.2 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.68 (d, J = 8.4 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 1 H), 7.84 (s, 1 H), 7.92-8.04 (m, 2 H). MS m/z 498 (M + H)+ 291

5-(4-(1H-indol-5-yl)-2-methylphenyl)-6- ((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.71 (m, 4 H), 1.29-1.44 (m, 1 H), 1.51-1.64 (m, 2 H), 1.71-1.84 (m, 2 H), 2.35 (s, 3 H), 2.54-2.69 (m, 1 H), 3.35- 3.44 (m, 1 H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 6.52 (br. s., 1 H), 7.40 (t, J = 2.6 Hz, 1 H), 7.44-7.54 (m, 3 H), 7.61-7.70 (m, 1 H), 7.73 (s, 1 H), 7.93 (s, 1 H), 11.19 (br. s., 1 H). MS m/z 453 (M + H)+ 292

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.71 (m, 4 H), 1.31-1.43 (m, 1 H), 1.54-1.65 (m, 2 H), 1.72-1.83 (m, 2 H), 2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J = 9.7, 5.6 Hz, 1 H), 3.65-3.82 (m, 4 H), 4.10 (s, 3 H), 4.12-4.22 (m, 1 H), 7.56 (d, J = 8.0 Hz, 1 H), 7.66-7.87 (m, 4 H), 8.13 (d, J = 3.6 Hz, 2 H). MS m/z 468 (M + H)+ 293

5-(4-(1H-indazol-5-yl)-2-methylphenyl)-6- ((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.71 (m, 4 H), 1.30-1.44 (m, 1 H), 1.53-1.65 (m, 2 H), 1.72-1.84 (m, 2 H), 2.36 (s, 3 H), 2.54-2.68 (m, 1 H), 3.36 (dd, J = 9.4, 5.4 Hz, 1 H), 3.64-3.81 (m, 4 H), 4.17 (t, J = 8.4 Hz, 1 H), 7.55 (d, J = 8.0 Hz, 1 H), 7.62-7.81 (m, 4 H), 8.15 (d, J = 3.6 Hz, 2 H), 13.16 (br. s., 1 H). MS m/z 454 (M + H)+ 294

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2-methylbenzofuran-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR) MHz, DMSO-d₆) δ ppm 0.54-0.71 (m, 4 H), 1.35-1.50 (m, 1 H), 1.50-1.65 (m, 3 H), 1.69-1.85 (m, 3 H), 2.26 (d, J = 7.0 Hz, 0.5 H), 2.40 (d, J = 7.3 Hz, 0.5 H), 2.90 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.05-3.30 (m, 2 H), 3.43-3.60 (m, 1.5 H), 3.77 (t, J = 6.6 Hz, 2 H), 6.66 (s, 1 H), 7.60 (s, 2 H), 7.75-7.83 (m, 2 H), 7.83-7.95 (m, 3 H). MS m/z 468 (M + H)+ 295

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 6.6 Hz, 4 H), 1.38-1.69 (m, 4 H), 1.70-1.95 (m, 3 H), 2.28 (t, J = 7.0 Hz, 0.5 H), 2.41 (d, J = 6.7 Hz, 0.5 H), 2.61 (s, 3 H), 2.84-2.98 (m, 0.5 H), 3.07-3.21 (m, 1 H), 3.21-3.30 (m, 0.5 H), 3.40- 3.67 (m, 2 H), 3.77 (t, J = 6.7 Hz, 2 H), 7.22 (s, 1 H), 7.67 (d, J = 8.4 Hz, 1 H), 7.78-7.86 (m, 2 H), 7.87-7.96 (m, 2 H), 7.99 (d, J = 8.4 Hz, 1 H), 8.12 (s, 1 H). MS m/z 484 (M + H)+ 296

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3- dimethylbenzo[b]thiophen-5-yl)phenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.40 (d, J = 6.2 Hz, 4 H), 1.24-1.41 (m, 4 H), 1.46-1.71 (m, 3 H), 2.03 (d, J = 6.9 Hz, 1 H), 2.13 (s, 3 H), 2.28 (s, 3 H), 2.67 (br. s., 0.5 H), 2.83-2.99 (m, 2 H), 3.19-3.38 (m, 1.5 H), 3.53 (t, J = 6.8 Hz, 2 H), 7.44 (d, J = 8.2 Hz, 1 H), 7.53-7.63 (m, 2 H), 7.66-7.81 (m, 4 H). MS m/z 498 (M + H)+ 297

(R)-5-(4-(1H-indazol-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.75 (m, 4 H), 1.36-1.50 (m, 1 H), 1.50-1.68 (m, 3 H), 1.69-1.96 (m, 3 H), 2.28 (t, J = 7.0 Hz, 1 H), 2.91 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07-3.31 (m, 2 H), 3.44- 3.64 (m, 1.5 H), 3.77 (t, J = 6.5 Hz, 2 H), 7.61-7.71 (m, 1 H), 7.73-7.85 (m, 3 H), 7.85-7.94 (m, 2 H), 8.16 (s, 2 H), 13.17 (br. s., 1 H). MS m/z 454 (M + H)+ 298

(R)-5-(4-(benzo[b]thiophen-5-yl)phenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.58-0.72 (m, 4 H), 1.38-1.69 (m, 4 H), 1.70-1.96 (m, 3 H), 2.29 (t, J = 6.9 Hz, 0.5 H), 2.37-2.49 (m, 0.5 H), 2.91 (dd, J = 11.9, 6.9 Hz, 0.5 H), 3.08-3.29 (m, 2 H), 3.39-3.63 (m, 1.5 H), 3.78 (t, J = 6.7 Hz, 2 H), 7.56 (d, J = 5.5 Hz, 1 H), 7.72- 7.87 (m, 4 H), 7.90-7.98 (m, 2 H), 8.14 (d, J = 8.4 Hz, 1 H), 8.29 (s, 1 H). MS m/z 470 (M + H)+ 299

5-(4-(1H-indol-6-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.73 (m, 4 H), 1.28-1.47 (m, 1 H), 1.61 (br. s., 2 H), 1.78 (br. s., 2 H), 2.72 (br. s., 1 H), 3.44 (d, J = 9.1 Hz, 1 H), 3.69- 3.89 (m, 2 H), 3.99 (d, J = 7.1 Hz, 2 H), 4.19 (t, J = 8.2 Hz, 1 H), 6.35-6.57 (m, 1 H), 7.43 (br. s., 2 H), 7.67 (d, J = 8.1 Hz, 1 H), 7.77 (d, J = 9.3 Hz, 3 H), 7.83-7.95 (m, 2 H), 11.21 (br. s., 1 H). MS m/z 439 (M + H)+ 300

5-(4-(1H-indazol-4-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62 (d, J = 5.1 Hz, 4 H), 1.30-1.45 (m, 1 H), 1.56-1.67 (m, 2 H), 1.75-1.87 (m, 2 H), 2.65-2.85 (m, 1 H), 3.46 (dd, J = 9.5, 5.5 Hz, 1 H), 3.73-3.86 (m, 2 H), 4.00 (d, J = 7.4 Hz, 2 H), 4.20 (t, J = 8.3 Hz, 1 H), 7.34 (d, J = 7.0 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.58-7.65 (m, 1 H), 7.85 (m, J = 8.2 Hz, 2 H), 7.93 (m, J = 8.2 Hz, 2 H), 8.24 (s, 1 H), 13.30 (s, 1 H). MS m/z 440 (M + H)+ 301

(R)-5-(4-(1H-indol-6-yl)phenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 5.9 Hz, 4 H), 1.34-1.51 (m, 1 H), 1.51-1.68 (m, 3 H), 1.69-1.95 (m, 3 H), 2.29 (d, J = 6.7 Hz, 1 H), 2.93 (m, 0.5 H), 3.07-3.25 (m, 1.5 H), 3.41-3.66 (m, 2 H), 3.78 (t, J = 6.8 Hz, 2 H), 6.48 (d, J = 2.7 Hz, 1 H), 7.34-7.48 (m, 2 H), 7.66 (d, J = 8.2 Hz, 1 H), 7.71-7.83 (m, 3 H), 7.83-7.93 (m, 2 H), 11.16 (br. s., 1 H). MS m/z 453 (M + H)+ 302

(R)-5-(4-(1H-indazol-4-yl)phenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.76 (m, 4 H), 1.45 (dd, J = 12.4, 7.6 Hz, 1 H), 1.53-1.70 (m, 3 H), 1.71-1.97 (m, 3 H), 2.25-2.38 (m, 1 H), 2.93 (dd, J = 11.8, 6.7 Hz, 0.5 H), 3.06-3.28 (m, 1.5 H), 3.44-3.67 (m, 2 H), 3.79 (t, J = 7.1 Hz, 2 H), 7.34 (d, J = 7.0 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 1 H), 7.81-7.98 (m, 4 H), 8.25 (d, J = 2.5 Hz, 1 H), 13.26 (br. s., 1 H). MS m/z 454 (M + H)+ 303

5-(4-(1H-indol-6-yl)-2-methylphenyl)-6- ((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.70 (m, 4 H), 1.37 (t, J = 6.2 Hz, 1 H), 1.53-1.64 (m, 2 H), 1.73-1.84 (m, 2 H), 2.54-2.73 (m, 1 H), 3.33-3.44 (m, 1 H), 3.64-3.82 (m, 4 H), 4.17 (t, J = 8.2 Hz, 1 H), 6.48 (br. s., 1 H), 7.35-7.45 (m, 2 H), 7.53 (d, J = 7.8 Hz, 1 H), 7.66 (dd, J = 8.0, 5.2 Hz, 2 H), 7.73 (s, 2 H), 11.20 (br. s., 1 H). MS m/z 453 (M + H)+ 304

5-(4-(1H-indazol-4-yl)-2-methylphenyl)-6- ((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.60 (d, J = 3.3 Hz, 4 H), 1.37 (quin, J = 6.3 Hz, 1 H), 1.56-1.67 (m, 2 H), 1.74-1.85 (m, 2 H), 2.39 (s, 3 H), 2.55-2.74 (m, 1 H), 3.38 (dd, J = 9.5, 5.5 Hz, 1 H), 3.64- 3.85 (m, 4 H), 4.18 (t, J = 8.4 Hz, 1 H), 7.32 (d, J = 7.0 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 1 H), 7.56-7.66 (m, 2 H), 7.68-7.76 (m, 1 H), 7.78 (s, 1 H), 8.25 (s, 1 H), 13.28 (br. s., 1 H). MS m/z 454 (M + H)+ 305

(R)-5-(4-(1H-indol-6-yl)-2-methylphenyl)- 6-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.74 (m, 4 H), 1.35-1.65 (m, 4 H), 1.69-1.94 (m, 3 H), 2.16-2.36 (m, 1 H), 2.38 (s, 3 H), 2.88 (dd, J = 11.9, 6.5 Hz, 0.5 H), 3.05-3.28 (m, 2 H), 3.41-3.64 (m, 3.5 H), 6.48 (d, J = 2.9 Hz, 1 H), 7.34- 7.46 (m, 2 H), 7.53 (dd, J = 13.3, 8.0 Hz, 1 H), 7.65 (d, J = 8.2 Hz, 2 H), 7.73 (s, 2 H), 11.19 (br. s., 1 H). MS m/z 467 (M + H)+ 306

(R)-5-(4-(1H-indazol-4-yl)-2- methylphenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65 (d, J = 6.5 Hz, 4 H), 1.36-1.52 (m, 1 H), 1.52-1.66 (m, 3 H), 1.70-1.95 (m, 3 H), 2.27 (br. s., 1 H), 2.41 (s, 3 H), 2.88 (dd, J = 11.8, 6.4 Hz, 0.5 H), 3.07-3.21 (m, 2 H), 3.44-3.54 (m, 2.5 H), 3.56- 3.65 (m, 1 H), 7.32 (d, J = 7.0 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 1 H), 7.55-7.67 (m, 2 H), 7.67-7.74 (m, 1 H), 7.76 (br. s., 1 H), 8.25 (s, 1 H), 13.24 (br. s., 1 H). MS m/z 468 (M + H)+ 307

(R)-5-(4-(benzo[d]oxazol-2-yl)phenyl)-6- ((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J = 5.1 Hz, 4 H), 1.36-1.68 (m, 4 H), 1.69-1.94 (m, 3 H), 2.16-2.44 (m, 1 H), 2.88 (dd, J = 11.7, 6.9 Hz, 0.5 H), 3.07- 3.31 (m, 2 H), 3.34-3.65 (m, 1.5 H), 3.77 (dd, J = 7.1, 3.6 Hz, 2 H), 7.39-7.56 (m, 2 H), 7.78-7.91 (m, 2 H), 7.97 (dd, J = 8.2, 4.3 Hz, 2 H), 8.36 (dd, J = 8.2, 1.8 Hz, 2 H). MS m/z 455 (M + H)+ 308

(R)-5-(4-(benzo[d]thiazol-2-yl)phenyl)-6- ((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 6.5 Hz, 4 H), 1.37-1.67 (m, 4 H), 1.69-1.96 (m, 3 H), 2.19-2.33 (m, 1 H), 2.90 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.05- 3.32 (m, 2 H), 3.36-3.64 (m, 1.5 H), 3.69-3.85 (m, 2 H), 7.52 (t, J = 7.4 Hz, 1 H), 7.60 (t, J = 7.4 Hz, 1 H), 7.93 (dd, J = 8.2, 4.6 Hz, 2 H), 8.12 (d, J = 8.0 Hz, 1 H), 8.21 (d, J = 7.8 Hz, 1 H), 8.24-8.34 (m, 2 H). MS m/z 471 (M + H)+ 309

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(quinolin-7-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.64 (d, J = 6.3 Hz, 4 H), 1.38-1.68 (m, 4 H), 1.70-1.98 (m, 3 H), 2.21-2.35 (m, 0.5 H), 2.35-2.48 (m, 0.5 H), 2.91 (dd, J = 11.8, 6.9 Hz, 0.5 H), 3.07-3.32 (m, 2 H), 3.44-3.64 (m, 1.5 H), 3.78 (t, J = 6.8 Hz, 2 H), 7.58 (dd, J = 8.2, 4.1 Hz, 1 H), 7.88 (dd, J = 8.2, 4.6 Hz, 2 H), 8.01-8.10 (m, 3 H), 8.10-8.18 (m, 1 H), 8.39 (s, 1 H), 8.44 (d, J = 8.0 Hz, 1 H), 8.98 (dd, J = 4.1, 1.4 Hz, 1 H). MS m/z 465 (M + H)+ 310

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(quinolin-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.75 (m, 4 H), 1.34-1.56 (m, 1 H), 1.56-1.68 (m, 3 H), 1.73-1.98 (m, 3 H), 2.33 (dt, J = 14.2, 7.2 Hz, 1 H), 2.91 (dd, J = 11.9, 6.8 Hz, 0.5 H), 3.09-3.32 (m, 2 H), 3.47-3.67 (m, 1.5 H), 3.73-3.86 (m, 2 H), 7.56 (dd, J = 8.5, 4.0 Hz, 1 H), 7.60- 7.72 (m, 3 H), 7.88 (dt, J = 7.9, 3.9 Hz, 3 H), 8.12 (d, J = 8.4 Hz, 1 H), 8.23 (t, J = 9.2 Hz, 1 H), 8.98 (d, J = 2.9 Hz, 1 H). MS m/z 465 (M + H)+ 311

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(6-fluoronaphthalen-2- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.74 (m, 4 H), 1.35-1.66 (m, 4 H), 1.70-1.96 (m, 3 H), 2.21-2.45 (m, 1 H), 2.90 (dd, J = 11.8, 7.0 Hz, 0.5 H), 3.07- 3.32 (m, 2 H), 3.42-3.64 (m, 1.5 H), 3.78 (t, J = 6.5 Hz, 2 H), 7.50 (td, J = 8.9, 2.5 Hz, 1 H), 7.78 (dd, J = 10.2, 2.3 Hz, 1 H), 7.86 (dd, J = 8.2, 4.1 Hz, 2 H), 7.95-8.09 (m, 4 H), 8.14 (dd, J = 9.1, 5.9 Hz, 1 H), 8.42 (s, 1 H). MS m/z 482 (M + H)+ 312

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(quinazolin-7-yl)phenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.80 (m, 2 H), 0.86-1.07 (m, 2 H), 1.48-1.58 (m, 1 H), 1.69-1.85 (m, 3 H), 1.86-1.97 (m, 2.5 H), 1.97-2.11 (m, 0.5 H), 2.37-2.70 (m, 1 H), 3.07 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.24-3.42 (m, 1 H), 3.51-3.91 (m, 4.5 H), 7.74-7.84 (m, 2 H), 7.87-7.96 (m, 2 H), 7.99 (dd, J = 8.5, 1.4 Hz, 1 H), 8.09 (d, J = 8.4 Hz, 1 H), 8.33 (s, 1 H), 9.41 (s, 1 H), 9.48 (s, 1 H). MS m/z 466 (M + H)+ 313

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(8-fluoronaphthalen-2- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.67 (m, 2 H), 0.87 (dt, J = 7.4, 3.7 Hz, 2 H), 1.35-1.47 (m, 1 H), 1.55- 1.75 (m, 3 H), 1.78-1.97 (m, 3 H), 2.28- 2.56 (m, 1 H), 2.99 (dd, J = 12.0, 7.0 Hz, 0.5 H), 3.13-3.31 (m, 1 H), 3.42-3.82 (m, 4.5 H), 7.13 (dd, J = 10.2, 7.9 Hz, 1 H), 7.31-7.42 (m, 1 H), 7.55-7.70 (m, 3 H), 7.75 (dd, J = 8.6, 1.4 Hz, 1 H), 7.82 (dd, J = 8.2, 4.5 Hz, 2 H), 7.90 (d, J = 8.5 Hz, 1 H), 8.28 (s, 1 H). MS m/z 482 (M + H)+ 314

(R)-5-(4-(1H-indol-3-yl)phenyl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63 (dd, J = 7.7, 3.0 Hz, 2 H), 0.77- 0.95 (m, 2 H), 1.38-1.48 (m, 1 H), 1.60- 1.73 (m, 3 H), 1.75-1.99 (m, 3 H), 2.29- 2.59 (m, 1 H), 3.01 (dd, J = 12.0, 6.9 Hz, 0.5 H), 3.14-3.31 (m, 1 H), 3.43-3.65 (m, 2.5 H), 3.66-3.85 (m, 2 H), 7.12- 7.27 (m, 2 H), 7.38 (dd, J = 7.3, 1.9 Hz, 2 H), 7.58 (dd, J = 8.1, 4.5 Hz, 2 H), 7.68- 7.80 (m, 2 H), 7.88 (d, J = 7.7 Hz, 1 H), 8.59 (br. s., 1 H). MS m/z 453 (M + H)+ 315

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(8-fluoroquinolin-7- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.72 (dd, J = 7.9, 3.1 Hz, 2 H), 0.92 (quin, J = 3.6 Hz, 2 H), 1.27-1.39 (m, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.81-2.97 (m, 1 H), 3.66 (dd, J = 9.9, 5.6 Hz, 1 H), 3.94-4.18 (m, 4 H), 4.27 (t, J = 8.2 Hz, 1 H), 7.55 (dd, J = 8.4, 4.3 Hz, 1 H), 7.63-7.72 (m, 1 H), 7.75 (d, J = 8.4 Hz, 3 H), 7.89 (d, J = 7.3 Hz, 2 H), 8.26 (d, J = 8.4 Hz, 1 H), 9.06 (dd, J = 4.1, 1.4 Hz, 1 H). MS m/z 469 (M + H)+ 316

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-methyl-4′-(1-methyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.67-0.82 (m, 2 H), 0.87-1.06 (m, 2 H), 1.44-1.57 (m, 1 H), 1.65 (dd, J = 12.6, 7.6 Hz, 0.5 H), 1.75-1.83 (m, 2.5 H), 1.84-1.91 (m, 2 H), 1.99 (dd, J = 12.4, 6.3 Hz, 1 H), 2.42 (s, 3 H), 2.53 (d, J = 8.2 Hz, 1 H), 2.99-3.04 (m, 0.5 H), 3.15- 3.38 (m, 1 H), 3.46-3.69 (m, 4.5 H), 3.99 (s, 3 H), 7.38-7.45 (m, 1 H), 7.55-7.67 (m, 6 H), 7.69 (s, 1 H), 7.83 (s, 1 H). MS m/z 508 (M + H)+ 317

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-methyl-4-(2-methyl-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.79 (m, 2 H), 0.89-1.04 (m, 2 H), 1.43-1.57 (m, 1 H), 1.66 (br. s., 1 H), 1.74-1.83 (m, 2.5 H), 1.83-1.91 (m, 2.5 H), 1.95-2.05 (m, 1 H), 2.41 (s, 3 H), 2.49 (s, 3 H), 3.04 (dd, J = 12.0, 6.5 Hz, 0.5 H), 3.14-3.20 (m, 0.5 H), 3.24-3.38 (m, 0.5 H), 3.48-3.71 (m, 4.5 H), 6.29 (s, 1 H), 7.34-7.45 (m, 3 H), 7.54-7.65 (m, 2 H), 7.78 (s, 1 H), 8.10 (br. s., 1 H). MS m/z 481 (M + H)+ 318

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3- yl)cyclopropanesulfonamide ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.80 (m, 2 H), 0.88-0.98 (m, 2 H), 1.01 (d, J = 7.7 Hz, 2 H), 1.18-1.29 (m, 2 H), 1.42-1.58 (m, 1.5 H), 1.65- 1.69 (m, 1 H), 1.77-1.87 (m, 2 H), 1.88- 1.97 (m, 2 H), 1.97-2.11 (m, 0.5 H), 2.35- 2.49 (m, 1 H), 2.49-2.65 (m, 1 H), 2.92- 3.01 (m, 0.5 H), 3.19-3.39 (m, 1 H), 3.44-3.78 (m, 4.5 H), 6.99 (br. s., 1 H), 7.33 (d, J = 7.1 Hz, 1 H), 7.37-7.49 (m, 3 H), 7.49-7.59 (m, 2 H), 7.59-7.68 (m, 1 H). MS m/z 551 (M + H)+ 319

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(2-methyl-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.86-1.03 (m, 2 H), 1.46-1.57 (m, 1 H), 1.57-1.74 (m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.92 (m, 2 H), 1.92-2.08 (m, 1 H), 2.50 (s, 3 H), 2.51-2.65 (m, 1 H), 3.03 (dd, J = 12.1, 7.0 Hz, 0.5 H), 3.16-3.37 (m, 1 H), 3.51- 3.79 (m, 4.5 H), 6.31 (s, 1 H), 7.38 (s, 2 H), 7.50 (dd, J = 11.2, 6.3 Hz, 1 H), 7.54- 7.64 (m, 2 H), 7.78 (s, 1 H), 8.15 (br. s., 1 H). MS m/z 485 (M + H)+ 320

5-(4-(6-chloronaphthalen-2-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.76 (m, 2 H), 0.86-0.97 (m, 2 H), 1.26-1.37 (m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.97 (m, 2 H), 2.81-2.98 (m, 1 H), 3.58 (dd, J = 9.9, 5.6 Hz, 1 H), 3.75- 3.87 (m, 1 H), 3.90-4.06 (m, 3 H), 4.27 (t, J = 8.3 Hz, 1 H), 7.52 (dd, J = 8.7, 2.0 Hz, 1 H), 7.56-7.63 (m, 1 H), 7.65-7.72 (m, 2 H), 7.78 (dd, J = 8.7, 1.8 Hz, 1 H), 7.84-7.94 (m, 3 H), 8.09 (s, 1 H). MS m/z 502 (M + H)+ 321

5-(4-(6-chloronaphthalen-2-yl)-2- methylphenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.39-0.48 (m, 2 H), 0.93-1.02 (m, 2 H), 1.19 (s, 3 H), 1.76-1.85 (m, 2 H), 1.85-1.94 (m, 2 H), 2.45 (s, 3 H), 2.68- 2.86 (m, 1 H), 3.76 (d, J = 7.4 Hz, 4 H), 4.13 (br. s., 2 H), 7.41-7.53 (m, 2 H), 7.65-7.73 (m, 2 H), 7.76-7.83 (m, 1 H), 7.83-7.93 (m, 3 H), 8.07 (s, 1 H). MS m/z 512 (M + H)+ 322

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-fluoro-4′-(1-methyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.75 (m, 2 H), 0.87-0.98 (m, 2 H), 1.25-1.37 (m, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.95 (m, 2 H), 2.78-2.97 (m, 1 H), 3.58 (dd, J = 9.8, 5.6 Hz, 1 H), 3.72- 3.86 (m, 1 H), 3.88-4.05 (m, 6 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1 H), 7.54-7.68 (m, 6 H), 7.70 (s, 1 H), 7.84 (s, 1 H). MS m/z 498 (M + H)+ 323

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-fluoro-4′-(1-methyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.78 (m, 2 H), 0.86-1.02 (m, 2 H), 1.40-1.65 (m, 2 H), 1.76-1.86 (m, 2 H), 1.86-1.93 (m, 2 H), 1.93-2.10 (m, 1 H), 2.37-2.65 (m, 1 H), 2.99 (dd, J = 12.0, 7.1 Hz, 0.5 H), 3.17-3.38 (m, 1 H), 3.47-3.65 (m, 2.5 H), 3.65-3.79 (m, 2 H), 3.95-4.06 (m, 3 H), 7.44-7.52 (m, 1 H), 7.53-7.68 (m, 6 H), 7.70 (s, 1 H), 7.84 (s, 1 H). MS m/z 512 (M + H)+ 324

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(7- fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.74 (m, 2 H), 0.86-0.96 (m, 2 H), 1.26-1.37 (m, 1 H), 1.77-1.87 (m, 2 H), 1.92 (quin, J = 3.7 Hz, 2 H), 2.78- 2.98 (m, 1 H), 3.60 (dd, J = 9.9, 5.6 Hz, 1 H), 3.76-3.89 (m, 1 H), 3.90-4.06 (m, 3 H), 4.27 (t, J = 8.3 Hz, 1 H), 7.24 (dd, J = 10.5, 7.8 Hz, 1 H), 7.49 (td, J = 7.9, 5.4 Hz, 1 H), 7.58-7.76 (m, 4 H), 7.81 (dd, J = 8.7, 1.6 Hz, 1 H), 8.01 (d, J = 8.7 Hz, 1 H), 8.37 (s, 1 H). MS m/z 486 (M + H)+ 325

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4′-(1-isopropyl-1H-pyrazol- 4-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.47 (dd, J = 7.2, 3.6 Hz, 2 H), 0.62- 0.74 (m, 2 H), 1.05 (td, J = 7.7, 3.4 Hz, 1 H), 1.31-1.42 (m, 6 H), 1.51-1.60 (m, 2 H), 1.61-1.70 (m, 2 H), 2.19 (s, 3 H), 2.44-2.62 (m, 1 H), 3.22-3.37 (m, 1 H), 3.41-3.52 (m, 1 H), 3.53-3.68 (m, 2 H), 3.73 (t, J = 9.1 Hz, 1 H), 3.99 (t, J = 8.2 Hz, 1 H), 4.34 (dt, J = 13.4, 6.7 Hz, 1 H), 7.18 (d, J = 7.8 Hz, 1 H), 7.29-7.47 (m, 6 H), 7.52 (s, 1 H), 7.62 (s, 1 H). MS m/z 522 (M + H)+ 326

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4′-(1-cyclopropyl-1H- pyrazol-4-yl)-3-methyl-[1,1′-biphenyl]-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.4, 3.8 Hz, 2 H), 0.86- 0.95 (m, 2 H), 1.03-1.13 (m, 2 H), 1.13- 1.27 (m, 2 H), 1.27-1.35 (m, 1 H), 1.75- 1.83 (m, 2 H), 1.83-1.92 (m, 2 H), 2.42 (s, 3 H), 2.68-2.85 (m, 1 H), 3.54 (dd, J = 10.9, 6.3 Hz, 1 H), 3.62-3.75 (m, 2 H), 3.77-3.91 (m, 2 H), 3.96 (t, J = 9.1 Hz, 1 H), 4.22 (t, J = 8.3 Hz, 1 H), 7.41 (d, J = 8.0 Hz, 1 H), 7.54-7.68 (m, 6 H), 7.78 (s, 1 H), 7.82 (s, 1 H). MS m/z 520 (M + H)+ 327

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-fluoro-4′-(1-isopropyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.4, 3.7 Hz, 2 H), 0.87- 0.97 (m, 2 H), 1.30 (td, J = 8.2, 3.9 Hz, 1 H), 1.60 (d, J = 6.7 Hz, 6 H), 1.76-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.77-2.97 (m, 1 H), 3.58 (dd, J = 9.7, 5.6 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H), 3.88-4.06 (m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 4.58 (dt, J = 13.4, 6.7 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1 H), 7.54-7.70 (m, 6 H), 7.76 (s, 1 H), 7.86 (s, 1 H). MS m/z 526 (M + H)+ 328

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4′-(1-cyclopropyl-1H- pyrazol-4-yl)-3-fluoro-[1,1′-biphenyl]-4-yl)- 4,6-diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.65-0.75 (m, 2 H), 0.87-0.97 (m, 2 H), 1.04-1.14 (m, 2 H), 1.17-1.24 (m, 2 H), 1.30 (td, J = 8.2, 4.0 Hz, 1 H), 1.77- 1.86 (m, 2 H), 1.86-1.95 (m, 2 H), 2.79- 2.97 (m, 1 H), 3.58 (dd, J = 9.7, 5.7 Hz, 1 H), 3.68 (dt, J = 7.3, 3.5 Hz, 1 H), 3.83 (d, J = 6.3 Hz, 1 H), 3.88-4.06 (m, 3 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1 H), 7.55-7.69 (m, 6 H), 7.79 (s, 1 H), 7.82 (s, 1 H). MS m/z 524 (M + H)+ 329

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3- fluoro-[1,1′-biphenyl]-4-yl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dt, J = 7.2, 3.7 Hz, 2 H), 0.86- 0.98 (m, 2 H), 1.30 (dq, J = 8.3, 4.0 Hz, 1 H), 1.77-1.85 (m, 2 H), 1.85-2.04 (m, 4 H), 2.47-2.72 (m, 4 H), 2.79-2.96 (m, 1 H), 3.58 (dd, J = 9.7, 5.7 Hz, 1 H), 3.74- 3.86 (m, 1 H), 3.88-4.07 (m, 3 H), 4.26 (t, J = 8.2 Hz, 1 H), 4.84 (quin, J = 8.3 Hz, 1 H), 7.49 (d, J = 11.7 Hz, 1 H), 7.55-7.69 (m, 6 H), 7.78 (s, 1 H), 7.87 (s, 1 H). MS m/z 538 (M + H)+ 330

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3- methyl-[1,1′-biphenyl]-4-yl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.3, 3.7 Hz, 2 H), 0.91 (t, J = 3.5 Hz, 2 H), 1.26-1.34 (m, 1 H), 1.75- 1.83 (m, 2 H), 1.83-2.01 (m, 4 H), 2.42 (s, 3 H), 2.48-2.68 (m, 4 H), 2.68-2.85 (m, 1 H), 3.52-3.60 (m, 1 H), 3.64-3.76 (m, 1 H), 3.77-3.92 (m, 2 H), 3.96 (t, J = 9.1 Hz, 1 H), 4.22 (t, J = 8.2 Hz, 1 H), 4.83 (t, J = 8.3 Hz, 1 H), 7.41 (d, J = 8.1 Hz, 1 H), 7.52-7.70 (m, 6 H), 7.77 (s, 1 H), 7.87 (s, 1 H). MS m/z 534 (M + H)+ 331

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4′-(1-isopropyl-1H-pyrazol- 4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.66 (m, 2 H), 0.79-0.87 (m, 2 H), 1.19-1.26 (m, 1 H), 1.49 (s, 3 H), 1.51 (s, 3 H), 1.66-1.75 (m, 2 H), 1.75- 1.84 (m, 2 H), 2.70-2.83 (m, 1 H), 3.53 (dd, J = 9.9, 5.6 Hz, 1 H), 3.82-4.06 (m, 4 H), 4.15 (t, J = 8.3 Hz, 1 H), 4.48 (quin, J = 6.7 Hz, 1 H), 7.49-7.61 (m, 6 H), 7.64- 7.73 (m, 3 H), 7.77 (s, 1 H). MS m/z 508 (M + H)+ 332

5-(4-(6-methoxynaphthalen-2-yl)-2- methylphenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.16-0.32 (m, 2 H), 0.74-0.83 (m, 2 H), 1.00 (s, 3 H), 1.55-1.65 (m, 2 H), 1.65-1.77 (m, 2 H), 2.25 (s, 3 H), 2.58 (d, J = 7.7 Hz, 1 H), 3.30-3.69 (m, 4 H), 3.79 (s, 3 H), 3.94 (br. s., 2 H), 6.97- 7.07 (m, 2 H), 7.25 (d, J = 7.8 Hz, 1 H), 7.46-7.58 (m, 3 H), 7.66 (t, J = 8.0 Hz, 2 H), 7.84 (s, 1 H). MS m/z 508 (M + H)+ 333

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-methyl-4′-(1-methyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.54-0.67 (m, 2 H), 0.76-0.86 (m, 2 H), 1.20 (td, J = 8.0, 4.4 Hz, 1 H), 1.65- 1.73 (m, 2 H), 1.75-1.82 (m, 2 H), 2.32 (s, 3 H), 2.60-2.75 (m, 1 H), 3.42-3.49 (m, 1 H), 3.54-3.66 (m, 1 H), 3.67-3.88 (m, 3 H), 3.89 (s, 3 H), 4.13 (t, J = 8.3 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.49 (d, J = 8.1 Hz, 4 H), 7.55 (d, J = 8.4 Hz, 2 H), 7.60 (s, 1 H), 7.74 (s, 1 H). MS m/z 494 (M + H)+ 334

5-(2-methyl-4-(6-methylnaphthalen-2- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.22-0.32 (m, 2 H), 0.76-0.87 (m, 2 H), 1.02 (s, 3 H), 1.59-1.68 (m, 2 H), 1.68-1.77 (m, 2 H), 2.28 (s, 3 H), 2.40 (s, 3 H), 2.50-2.67 (m, 1 H), 3.60 (d, J = 7.4 Hz, 4 H), 3.97 (br. s., 2 H), 7.19- 7.32 (m, 2 H), 7.48-7.60 (m, 4 H), 7.63- 7.75 (m, 2 H), 7.89 (s, 1 H). MS m/z 492 (M + H)+ 335

5-(2-methyl-4-(1-methyl-1H-indazol-6- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29-0.40 (m, 2 H), 0.83-0.93 (m, 2 H), 1.10 (s, 3 H), 1.65-1.74 (m, 2 H), 1.75-1.84 (m, 2 H), 2.35 (s, 3 H), 2.67 (br. s., 1 H), 3.54 (br. s., 1 H), 3.66 (d, J = 7.3 Hz, 4 H), 4.07 (s, 5 H), 7.34 (t, J = 7.8 Hz, 2 H), 7.48-7.60 (m, 3 H), 7.73 (d, J = 8.4 Hz, 1 H), 7.94 (s, 1 H). MS m/z 482 (M + H)+ 336

5-(2-methyl-4-(2-methyl-2H-indazol-6- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.37-0.49 (m, 2 H), 0.92-1.02 (m, 2 H), 1.19 (s, 3 H), 1.75-1.83 (m, 2 H), 1.83-1.92 (m, 2 H), 2.43 (s, 3 H), 2.68- 2.83 (m, 1 H), 3.76 (d, J = 7.6 Hz, 4 H), 4.13 (br. s., 2 H), 4.27 (s, 3 H), 7.33- 7.47 (m, 2 H), 7.60-7.69 (m, 2 H), 7.76 (d, J = 8.8 Hz, 1 H), 7.94 (d, J = 6.9 Hz, 2 H). MS m/z 482 (M + H)+ 337

5-(4′-(1-cyclopropyl-1H-pyrazol-4-yl)-3- methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.22-0.32 (m, 2 H), 0.77-0.85 (m, 2 H), 0.87-0.96 (m, 2 H), 0.99-1.10 (m, 5 H), 1.58-1.67 (m, 2 H), 1.68-1.75 (m, H), 2.26 (s, 3 H), 2.49-2.68 (m, 1 H), 3.38-3.73 (m, 5 H), 3.96 (br. s., 2 H), 7.25 (d, J = 8.0 Hz, 1 H), 7.45 (q, J = 8.3 Hz, 6 H), 7.62 (s, 1 H), 7.66 (s, 1 H). MS m/z 534 (M + H)+ 338

5-(4′-(1-cyclobutyl-1H-pyrazol-4-yl)-3- methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29-0.38 (m, 2 H), 0.84-0.91 (m, 2 H), 1.09 (s, 3 H), 1.64-1.73 (m, 2 H), 1.78 (t, J = 3.4 Hz, 2 H), 1.79-1.90 (m, 2 H), 2.32 (s, 3 H), 2.38-2.58 (m, 4 H), 2.58-2.71 (m, 1 H), 3.53 (d, J = 6.7 Hz, 1 H), 3.65 (d, J = 7.4 Hz, 4 H), 4.02 (br. s., 2 H), 4.74 (quin, J = 8.4 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.44-7.59 (m, 6 H), 7.68 (s, 1 H), 7.77 (s, 1 H). MS m/z 548 (M + H)+ 339

5-(4-(3-chloroquinolin-7-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.75 (m, 2 H), 0.86-0.97 (m, 2 H), 1.30 (td, J = 8.2, 4.1 Hz, 1 H), 1.76- 1.85 (m, 2 H), 1.86-1.95 (m, 2 H), 2.77- 2.96 (m, 1 H), 3.63 (dd, J = 9.9, 5.5 Hz, 1 H), 3.90-4.06 (m, 3 H), 4.06-4.17 (m, 1 H), 4.26 (t, J = 8.3 Hz, 1 H), 7.75 (d, J = 8.2 Hz, 2 H), 7.86-7.97 (m, 4 H), 8.21 (d, J = 2.3 Hz, 1 H), 8.38 (s, 1 H), 8.89 (d, J = 2.5 Hz, 1 H). MS m/z 485 (M + H)+ 340

5-(4-(3-chloroquinolin-7-yl)-2- methylphenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29-0.39 (m, 2 H), 0.84-0.92 (m, 2 H), 1.10 (s, 3 H), 1.72 (t, J = 3.5 Hz, 2 H), 1.75-1.84 (m, 2 H), 2.36 (s, 3 H), 2.60-2.74 (m, 1 H), 3.67 (d, J = 7.4 Hz, 4 H), 4.06 (dt, J = 14.4, 7.3 Hz, 2 H), 7.40 (d, J = 7.7 Hz, 1 H), 7.58-7.68 (m, 2 H), 7.79 (s, 2 H), 8.11 (d, J = 2.1 Hz, 1 H), 8.27 (s, 1 H), 8.80 (d, J = 2.3 Hz, 1 H). MS m/z 513 (M + H)+ 341

(R)-5-(5-(1H-indol-5-yl)pyridin-2-yl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.18-0.34 (m, 2 H), 0.44 (d, J = 4.3 Hz, 2 H), 1.03-1.30 (m, 2 H), 1.30-1.37 (m, 2 H), 1.39-1.48 (m, 2 H), 1.61 (m, J = 19.0, 12.5, 6.4, 6.4 Hz, 1 H), 2.22- 2.39 (m, 0.5 H), 2.39-2.52 (m, 0.5 H), 2.72-2.83 (m, 0.5 H), 2.89-3.02 (m, 1 H), 3.11-3.25 (m, 1.5 H), 3.26-3.43 (m, 1 H), 3.73-4.04 (m, 2 H), 6.13 (br. s., 1 H), 6.80-6.92 (m, 1 H), 7.03 (d, J = 8.7 Hz, 1 H), 7.13 (d, J = 8.4 Hz, 1 H), 7.50 (s, 1 H), 7.62-7.72 (m, 1 H), 7.72-7.81 (m, 1 H), 8.53 (s, 1 H), 10.35 (br. s., 1 H). MS m/z 454 (M + H)+ 342

(R)-5-(5-(benzo[b]thiophen-5-yl)pyridin-2- yl)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.69 (m, 2 H), 0.82-0.96 (m, 2 H), 1.55-1.73 (m, 2 H), 1.73-1.79 (m, 2 H), 1.80-1.86 (m, 2 H), 1.87-2.08 (m, 1 H), 2.67 (dt, J = 15.1, 7.4 Hz, 0.5 H), 2.74-2.89 (m, 0.5 H), 3.07-3.23 (m, 0.5 H), 3.27-3.38 (m, 1 H), 3.48-3.76 (m, 2.5 H), 4.12 (dd, J = 13.5, 8.4 Hz, 1 H), 4.21-4.42 (m, 2 H), 7.37 (d, J = 5.4 Hz, 1 H), 7.48 (d, J = 5.5 Hz, 1 H), 7.55 (d, J = 8.5 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H), 7.99- 8.08 (m, 2 H), 8.11-8.21 (m, 1 H), 8.89 (br. s., 1 H). MS m/z 471 (M + H)+ 343

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.65 (m, 2 H), 0.76-0.87 (m, 2 H), 1.19-1.26 (m, 1 H), 1.68-1.74 (m, 2 H), 1.75-1.84 (m, 2 H), 2.69-2.86 (m, 1 H), 3.55 (dd, J = 9.8, 5.6 Hz, 1 H), 3.83 (s, 3 H), 3.85-4.07 (m, 4 H), 4.16 (t, J = 8.3 Hz, 1 H), 7.35-7.47 (m, 1 H), 7.49- 7.63 (m, 3 H), 7.74 (d, J = 8.2 Hz, 2 H), 7.86 (s, 1 H), 7.99 (s, 1 H). MS m/z 454 (M + H)+ 344

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-methyl-1H-indol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.53-0.67 (m, 2 H), 0.76-0.88 (m, 2 H), 1.19-1.26 (m, 1 H), 1.64-1.74 (m, 2 H), 1.74-1.84 (m, 2 H), 2.66-2.86 (m, 1 H), 3.55 (dd, J = 9.8, 5.5 Hz, 1 H), 3.77 (s, 3 H), 3.81-4.07 (m, 4 H), 4.14 (t, J = 8.3 Hz, 1 H), 6.49 (d, J = 2.9 Hz, 1 H), 7.04 (d, J = 3.0 Hz, 1 H), 7.34 (d, J = 8.5 Hz, 1 H), 7.39-7.49 (m, 1 H), 7.56 (m, J = 8.2 Hz, 2 H), 7.73 (m, J = 8.1 Hz, 2 H), 7.82 (s, 1 H). MS m/z 453 (M + H)+ 345

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(quinolin-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.6, 3.2 Hz, 2 H), 0.91 (br. s., 2 H), 1.30 (td, J = 8.0, 3.9 Hz, 1 H), 1.75-1.86 (m, 2 H), 1.86-1.97 (m, 2 H), 2.72-2.93 (m, 1 H), 3.62 (dd, J = 9.5, 5.6 Hz, 1 H), 3.88-4.17 (m, 4 H), 4.24 (t, J = 8.1 Hz, 1 H), 7.49-7.66 (m, 1 H), 7.70- 7.84 (m, 3 H), 7.89 (d, J = 8.0 Hz, 1 H), 7.96 (d, J = 8.5 Hz, 1 H), 8.21 (d, J = 8.4 Hz, 1 H), 8.27-8.46 (m, 3 H). MS m/z 451 (M + H)+ 346

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(quinolin-7- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.42-0.54 (m, 2 H), 0.69 (dt, J = 7.2, 3.4 Hz, 2 H), 1.05-1.12 (m, 1 H), 1.54- 1.65 (m, 2 H), 1.65-1.75 (m, 2 H), 2.61- 2.76 (m, 1 H), 3.38 (dd, J = 9.9, 5.6 Hz, 1 H), 3.55-3.68 (m, 1 H), 3.68-3.85 (m, 3 H), 4.06 (t, J = 8.3 Hz, 1 H), 7.27 (dd, J = 8.2, 4.3 Hz, 1 H), 7.38-7.56 (m, 3 H), 7.57-7.67 (m, 1 H), 7.76 (d, J = 8.5 Hz, 1 H), 8.02 (d, J = 8.1 Hz, 1 H), 8.17 (s, 1 H), 8.69-8.86 (m, 1 H). MS m/z 469 (M + H)+ 347

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61 (br. s., 2 H), 0.82 (br. s., 2 H), 1.16-1.27 (m, 1 H), 1.73 (br. s., 2 H), 1.81 (br. s., 2 H), 2.79 (br. s., 1 H), 3.43- 3.56 (m, 1 H), 3.76 (br. s., 1 H), 3.80- 3.97 (m, 3 H), 4.06 (s, 3 H), 4.18 (t, J = 8.1 Hz, 1 H), 7.35-7.48 (m, 2 H), 7.48-7.65 (m, 3 H), 7.90 (br. s., 1 H), 7.99 (s, 1 H). MS m/z 472 (M + H)+ 348

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.3, 3.7 Hz, 2 H), 0.78- 0.87 (m, 2 H), 1.21 (td, J = 8.0, 4.0 Hz, 1 H), 1.69-1.77 (m, 2 H), 1.77-1.88 (m, 2 H), 2.72-2.87 (m, 1 H), 3.51 (dd, J = 9.8, 5.6 Hz, 1 H), 3.68-3.80 (m, 1 H), 3.84 (s, 3 H), 3.85-3.97 (m, 3 H), 4.18 (t, J = 8.4 Hz, 1 H), 7.39-7.49 (m, 2 H), 7.49-7.58 (m, 3 H), 7.88 (s, 1 H), 7.98 (s, 1 H). MS m/z 472 (M + H)+ 349

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6- fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.66 (m, 2 H), 0.77-0.87 (m, 2 H), 1.19-1.27 (m, 1 H), 1.69-1.77 (m, 2 H), 1.79-1.87 (m, 2 H), 2.74-2.88 (m, 1 H), 3.49 (dd, J = 9.9, 5.6 Hz, 1 H), 3.68- 3.79 (m, 1 H), 3.82-3.97 (m, 3 H), 4.19 (t, J = 8.4 Hz, 1 H), 7.27 (td, J = 8.7, 2.4 Hz, 1 H), 7.40-7.53 (m, 2 H), 7.53-7.64 (m, 2 H), 7.71 (s, 1 H), 7.79-7.91 (m, 2 H), 8.02 (s, 1 H). MS m/z 486 (M + H)+ 350

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(8- fluoronaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61 (dd, J = 7.1, 4.0 Hz, 2 H), 0.77- 0.88 (m, 2 H), 1.19-1.26 (m, 1 H), 1.68- 1.78 (m, 2 H), 1.78-1.89 (m, 2 H), 2.71- 2.89 (m, 1 H), 3.51 (dd, J = 9.8, 5.6 Hz, 1 H), 3.67-3.80 (m, 1 H), 3.80-3.98 (m, 3 H), 4.19 (t, J = 8.3 Hz, 1 H), 7.08-7.17 (m, 1 H), 7.40 (td, J = 7.9, 5.6 Hz, 1 H), 7.50- 7.67 (m, 4 H), 7.68-7.76 (m, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 8.28 (s, 1 H). MS m/z 486 (M + H)+ 351

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(6- methoxynaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.65 (m, 2 H), 0.78-0.86 (m, 2 H), 1.20-1.27 (m, 1 H), 1.68-1.78 (m, 2 H), 1.82 (quin, J = 3.7 Hz, 2 H), 2.71- 2.87 (m, 1 H), 3.50 (dd, J = 9.9, 5.6 Hz, 1 H), 3.68-3.79 (m, 1 H), 3.80-3.97 (m, 6 H), 4.18 (t, J = 8.3 Hz, 1 H), 7.08-7.17 (m, 2 H), 7.46-7.66 (m, 4 H), 7.77 (t, J = 9.1 Hz, 2 H), 7.95 (s, 1 H). MS m/z 498 (M + H)+ 352

5-(2-fluoro-4-(2-methylbenzo[b]thiophen- 5-yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM- d) δ ppm 0.44 (br. s., 2 H), 0.99 (br. s., 2 H), 1.20 (s, 3 H), 1.82 (br. s., 2 H), 1.90 (br. s., 2 H), 2.65 (s, 3 H), 2.85 (br. s., 1 H), 3.86 (br. s., 4 H), 4.17 (br. s., 2 H), 7.07 (s, 1 H), 7.46-7.58 (m, 2 H), 7.58- 7.68 (m, 2 H), 7.83-7.96 (m, 2 H). MS m/z 502 (M + H)+ 353

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2- methylbenzofuran-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.73 (m, 4 H), 1.32-1.45 (m, 1 H), 1.57-1.69 (m, 2 H), 1.77-1.89 (m, 2 H), 2.59-2.77 (m, 1 H), 3.41 (dd, J = 9.8, 5.8 Hz, 1 H), 3.69-3.90 (m, 4 H), 4.18 (t, J = 8.4 Hz, 1 H), 6.66 (s, 1 H), 7.57-7.86 (m, 5 H), 7.97 (s, 1 H). MS m/z 472 (M + H)+ 354

(R)-5-(2-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.59-0.95 (m, 4 H), 1.47 (br. s., 2 H), 1.67-1.75 (m, 2 H), 1.77-1.90 (m, 3 H), 2.29-2.43 (m, 1 H), 2.55 (s, 3 H), 2.97 (br. s., 1 H), 3.41 (br. s., 2 H), 3.57 (br. s., 2.5 H), 3.71 (br. s., 0.5 H), 6.97 (s, 1 H), 7.36-7.47 (m, 2 H), 7.48-7.58 (m, 2 H), 7.77 (d, J = 8.4 Hz, 1 H), 7.79-7.87 (m, 1 H). MS m/z 518 (M + H)+ 355

(R)-5-(2-fluoro-4-(2-methylbenzofuran-5- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.79 (br. s., 2 H), 0.91-1.05 (m, 1 H), 1.11 (br. s., 1 H), 1.36 (br. s., 2 H), 1.66-1.74 (m, 2 H), 1.76-1.90 (m, 3 H), 2.27-2.39 (m, 1 H), 2.95 (br s., 0.5 H), 3.17-3.50 (m, 2 H), 3.57 (br. s., 2.5 H), 3.71 (br. s., 1 H), 6.36 (s, 1 H), 7.33- 7.44 (m, 3 H), 7.44-7.56 (m, 2 H), 7.63 (s, 1 H). MS m/z 502 (M + H)+ 356

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2- methylbenzo[d]thiazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.75 (m, 2 H), 0.87-0.96 (m, 2 H), 1.26-1.37 (m, 1 H), 1.76-1.86 (m, 2 H), 1.86-1.96 (m, 2 H), 2.83-2.96 (m, 4 H), 3.60 (dd, J = 9.8, 5.7 Hz, 1 H), 3.85 (d, J = 6.3 Hz, 1 H), 3.91-4.06 (m, 3 H), 4.27 (t, J = 8.3 Hz, 1 H), 7.28 (s, 2 H), 7.54 (d, J = 11.5 Hz, 1 H), 7.60-7.70 (m, 3 H), 7.96 (d, J = 8.2 Hz, 1 H), 8.21 (d, J = 1.4 Hz, 1 H). MS m/z 489 (M + H)+ 357

5-(2-fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.24-0.34 (m, 2 H), 0.78-0.89 (m, 2 H), 1.05 (s, 3 H), 1.61-1.70 (m, 2 H), 1.70-1.81 (m, 2 H), 2.61-2.78 (m, 1 H), 3.70 (br. s., 4 H), 4.00 (br. s., 5 H), 7.31- 7.42 (m, 2 H), 7.42-7.57 (m, 3 H), 7.84 (s, 1 H), 7.93 (s, 1 H). MS m/z 486 (M + H)+ 358

5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)- [1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.40-0.49 (m, 2 H), 0.93-1.03 (m, 2 H), 1.20 (s, 3 H), 1.76-1.85 (m, 2 H), 1.86-1.96 (m, 2 H), 2.78-2.92 (m, 1 H), 3.81-3.94 (m, 3 H), 4.00 (br. s.,, 4 H), 4.16 (br. s., 2 H), 7.49 (d, J = 11.5 Hz, 1 H), 7.55-7.67 (m, 6 H), 7.71 (s, 1 H), 7.84 (s, 1 H). MS m/z 512 (M + H)+ 359

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.24-0.34 (m, 2 H), 0.80-0.88 (m, 2 H), 1.06 (s, 3 H), 1.62-1.72 (m, 2 H), 1.72-1.82 (m, 2 H), 2.62-2.80 (m, 1 H), 3.52 (br. s., 1 H), 3.57-3.82 (m, 3 H), 4.00 (br. s., 2 H), 7.16-7.26 (m, 1 H), 7.34-7.48 (m, 2 H), 7.48-7.57 (m, 2 H), 7.64 (s, 1 H), 7.73-7.85 (m, 2 H), 7.95 (s, 1 H). MS m/z 500 (M + H)+ 361

(R)-5-(2-fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.44-0.58 (m, 2 H), 0.80-0.99 (m, 2 H), 1.52-1.73 (m, 2 H), 1.78-1.87 (m, 2 H), 1.87-2.03 (m, 3 H), 2.50 (dt, J = 14.6, 7.3 Hz, 1 H), 2.96-3.12 (m, 1.5 H), 3.66-3.80 (m, 3.5 H), 4.15 (s, 3 H), 7.45-7.56 (m, 2 H), 7.58-7.72 (m, 3 H), 7.99 (s, 1 H), 8.09 (s, 1 H). MS m/z 500 (M + H)+ 362

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-5- yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.52 (s, 2 H), 0.76-1.02 (m, 2 H), 1.23-1.28 (m, 3 H), 1.48-1.70 (m, 2 H), 1.75-1.87 (m, 2 H), 1.88-2.05 (m, 3 H), 2.40-2.59 (m, 1 H), 3.06 (br. s., 1 H), 3.27-3.48 (m, 1 H), 3.69 (br. s., 3 H), 3.97 (s, 3 H), 6.40 (d, J = 1.8 Hz, 1 H), 7.51 (d, J = 11.3 Hz, 1 H), 7.55-7.71 (m, 5 H), 7.74 (d, J = 8.2 Hz, 2 H). MS m/z 526 (M + H)+ 363

(R)-5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.35-0.46 (m, 2 H), 0.68-0.92 (m, 2 H), 1.09-1.16 (m, 3 H), 1.51 (br. s., 1 H), 1.65-1.78 (m, 2 H), 1.78-1.89 (m, 3 2.40 (dt, J = 14.5, 7.3 Hz, 1 H), 2.98 (br. s., 1 H), 3.20-3.52 (m, 2.5 H), 3.60 (br. s., 2.5 H), 7.20-7.30 (m, 1 H), 7.38- 7.53 (m, 2 H), 7.54-7.62 (m, 2 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.78-7.89 (m, 2 H), 8.00 (s, 1 H). MS m/z 514 (M + H)+ 364

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.34-0.48 (m, 2 H), 0.70-0.90 (m, 2 H), 1.14 (s, 3 H), 1.51 (br. s., 1 H), 1.68- 1.76 (m, 2 H), 1.77-1.90 (m, 3 H), 2.39 (dt, J = 14.3, 7.2 Hz, 1 H), 2.98 (br. s., 1 H), 3.40 (br. s., 2.5 H), 3.52-3.68 (m, 2.5 H), 3.90 (s, 3 H), 7.39 (d, J = 11.3 Hz, 1 H), 7.45-7.59 (m, 6 H), 7.61 (s, 1 H), 7.75 (s, 1 H). MS m/z 526 (M + H)+ 365

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.83 (d, J = 2.7 Hz, 2 H), 1.19 (br. s., 2 H), 1.67-1.77 (m, 2 H), 1.77-1.86 (m, 2 H), 2.68-2.84 (m, 1 H), 3.49-3.66 (m, 1 H), 3.80 (br. s., 2 H), 4.00 (br. s., 2 H), 4.36 (br. s., 1 H), 7.27 (td, J = 8.8, 2.3 Hz, 1 H), 7.39-7.53 (m, 2 H), 7.54-7.62 (m, 2 H), 7.70 (s, 1 H), 7.78-7.90 (m, 2 H), 8.01 (s, 1 H). MS m/z 502 (M + H)+ 366

5-(2-fluoro-4-(6-methoxynaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.91 (m, 2 H), 1.65 (br. s., 1 H), 1.72 (br. s., 1 H), 1.81 (br. s., 2 H), 1.96 (br. s., 2 H), 2.73 (br. s., 1 H), 3.27- 3.65 (m, 3 H), 3.70-4.09 (m, 6 H), 4.19- 4.58 (m, 1 H), 7.03-7.28 (m, 2 H), 7.39- 7.61 (m, 3 H), 7.64 (br. s., 1 H), 7.77 (br. s., 2 H), 7.95 (br. s., 1 H). MS m/z 514 (M + H)+ 368

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(naphthalen-2- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.72 (br. s., 2 H), 0.92 (br. s., 2 H), 1.32 (br. s., 1 H), 1.84 (br. s., 2 H), 1.92 (br. s., 2 H), 2.90 (br. s., 1 H), 3.61 (br. s., 1 H), 3.86 (br. s., 1 H), 3.98 (br. s., 3 H), 4.28 (br. s., 1 H), 7.59 (br. s., 5 H), 7.95 (br. s., 4 H), 8.13 (br. s., 1 H). MS m/z 468 (M + H)+ 369

5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(oxetane-2- carbonyl)azetidin-3-yl)methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.75-1.86 (m, 2 H), 1.86-1.97 (m, 2 H), 2.69-3.03 (m, 3 H), 3.62-3.74 (m, 1 H), 3.79-3.96 (m, 2 H), 4.02-4.16 (m, 2 H), 4.21-4.32 (m, 1 H), 4.47-4.70 (m, 2 H), 5.06-5.20 (m, 1 H), 7.36 (td, J = 8.7, 2.5 Hz, 1 H), 7.49-7.63 (m, 2 H), 7.64- 7.72 (m, 2 H), 7.78 (d, J = 7.8 Hz, 1 H), 7.88-7.99 (m, 2 H), 8.11 (s, 1 H). MS m/z 502 (M + H)+ 370

(R)-5-(2-fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.72-0.85 (m, 2 H), 0.88-1.01 (m, 1 H), 1.05 (br. s., 1 H), 1.46 (br. s., 1.5 H), 1.64-1.76 (m, 2.5 H), 1.76-1.92 (m, 3 H), 2.28-2.46 (m, 1 H), 2.96 (br. s., 0.5 H), 3.27 (br. s., 1 H), 3.57 (br. s., 3 H), 3.71 (br. s., 1.5 H), 4.05 (s, 3 H), 7.33- 7.46 (m, 2 H), 7.47-7.63 (m, 3 H), 7.90 (s, 1 H), 7.98 (s, 1 H). MS m/z 502 (M + H)+ 371

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-5- yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.72-0.87 (m, 2 H), 0.91-1.14 (m, 2 H), 1.43 (br. s., 1 H), 1.67-1.77 (m, 2 H), 1.78-1.89 (m, 3 H), 2.27-2.44 (m, 1 H), 2.95 (br. s., 0.5 H), 3.29 (br. s., 2 H), 3.50-3.67 (m, 2.5 H), 3.78 (br. s., 1 H), 3.87 (s, 4 H), 6.30 (d, J = 1.6 Hz, 1 H), 7.42 (d, J = 11.1 Hz, 1 H), 7.45-7.61 (m, 5 H), 7.64 (d, J = 8.2 Hz, 2 H). MS m/z 528 (M + H)+ 372

5-(2-fluoro-4-(naphthalen-2-yl)phenyl)-6- ((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.82 (br. s., 2 H), 1.13 (br. s., 2 H), 1.72 (br. s., 2 H), 1.81 (br. s., 2 H), 2.61- 2.84 (m, 1 H), 3.07 (br. s., 1 H), 3.57 (br. s., 1 H), 3.80 (br. s., 2 H), 3.97 (br. s., 2 H), 4.38 (br. s., 1 H), 7.41-7.72 (m, 6 H), 7.76-7.96 (m, 3 H), 8.02 (s, 1 H). MS m/z 484 (M + H)+ 373

6-(3-fluoro-4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.85 (br. s., 2 H), 1.17-1.28 (m, 2 H), 1.69-1.78 (m, 2 H), 1.78-1.88 (m, 2 H), 2.77 (br. s., 1 H), 3.57 (br. s., 1 H), 3.71-3.88 (m, 2 H), 4.00 (br. s., 2 H), 4.35 (br. s., 1 H), 7.52 (d, J = 10.7 Hz, 1 H), 7.56-7.66 (m, 3 H), 7.76-7.84 (m, 1 H), 7.90-8.01 (m, 2 H), 8.06 (s, 1 H), 8.22 (s, 1 H). MS m/z 509 (M + H)+ 374

5-(2-fluoro-4-(8-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.83 (d, J = 3.0 Hz, 2 H), 1.14-1.21 (m, 2 H), 1.67-1.77 (m, 2 H), 1.77-1.89 (m, 2 H), 2.64-2.88 (m, 2 H), 3.57 (br. s., 1 H), 3.80 (br. s., 2 H), 4.00 (br. s., 2 H), 4.38 (br. s., 1 H), 7.15 (dd, J = 10.4, 7.9 Hz, 1 H), 7.40 (td, J = 7.9, 5.4 Hz, 1 H), 7.48-7.67 (m, 4 H), 7.72 (dd, J = 8.6, 1.7 Hz, 1 H), 7.90 (s, 1 H), 8.28 (s, 1 H). MS m/z 502 (M + H)+ 375

5-(2-fluoro-4-(8-methoxynaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.82 (br. s., 2 H), 1.14 (br. s., 2 H), 1.72 (br. s., 2 H), 1.81 (br. s., 2 H), 2.73 (br. s., 1 H), 2.90 (br. s., 1 H), 3.57 (br. s., 1 H), 3.67-3.85 (m, 2 H), 3.85-4.11 (m, 5 H), 4.35 (br. s., 1 H), 6.80 (br. s., 1 H), 7.39 (br. s., 2 H), 7.46-7.59 (m, 2 H), 7.59-7.72 (m, 2 H), 7.84 (d, J = 8.4 Hz, 1 H), 8.46 (br. s., 1 H). MS m/z 514 (M + H)+ 377

5-(2-fluoro-4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.39-0.51 (m, 2 H), 0.64-0.75 (m, 2 H), 1.38 (d, J = 3.7 Hz, 2 H), 1.57 (d, J = 3.6 Hz, 2 H), 2.34-2.51 (m, 1 H), 3.18 (br. s., 1 H), 3.53 (br. s., 3 H), 3.65 (s, 3 H), 3.79 (br. s., 1 H), 4.04-4.21 (m, 1 H), 7.40- 7.66 (m, 6 H), 7.87 (s, 1 H), 8.03 (s, 1 H). MS m/z 488 (M + H)+ 378

5-(2-fluoro-4-(1-methyl-1H- benzo[d]imidazol-5-yl)phenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.29-0.39 (m, 2 H), 0.89 (br. s., 2 H), 1.67-1.76 (m, 2 H), 1.77-1.85 (m, 2 H), 2.65-2.83 (m, 1 H), 3.50-3.82 (m, 4 H), 3.83 (s, 3 H), 4.06 (br. s., 2 H), 7.37- 7.48 (m, 2 H), 7.48-7.59 (m, 3 H), 7.87 (s, 1 H), 7.97 (s, 1 H). MS m/z 486 (M + H)+ 379

(R)-5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.69-0.85 (m, 2 H), 0.88-0.99 (m, 1 H), 1.03 (br. s., 1 H), 1.28-1.55 (m, 1 H), 1.66-1.76 (m, 2 H), 1.76-1.89 (m, 3 H), 2.34 (dt, J = 14.2, 7.1 Hz, 0.5 H), 3.29 (br. s., 2 H), 3.49-3.66 (m, 2.5 H), 3.75 (br. s., 1 H), 3.89 (s, 3 H), 3.96-4.17 (m, 1 H), 7.38 (d, J = 11.3 Hz, 1 H), 7.43-7.58 (m, 6 H), 7.60 (s, 1 H), 7.74 (s, 1 H). MS m/z 528 (M + H)+ 380

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(8- methoxynaphthalen-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.77 (m, 2 H), 0.91 (br. s., 2 H), 1.30 (dd, J = 7.8, 3.6 Hz, 1 H), 1.82 (br. s., 2 H), 1.91 (br. s., 2 H), 2.78-2.99 (m, 1 H), 3.60 (dd, J = 9.1, 5.6 Hz, 1 H), 3.77- 3.88 (m, 1 H), 3.88-4.03 (m, 3 H), 4.07 (s, 3 H), 4.26 (t, J = 8.2 Hz, 1 H), 6.90 (d, J = 4.3 Hz, 1 H), 7.41-7.53 (m, 2 H), 7.57- 7.69 (m, 2 H), 7.69-7.81 (m, 2 H), 7.93 (d, J = 8.5 Hz, 1 H), 8.55 (s, 1 H). MS m/z 498 (M + H)+ 381

(R)-5-(2-fluoro-4-(6-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.00 (br. s., 2 H), 0.11-0.31 (m, 2 H), 0.62-0.76 (m, 1 H), 0.86-0.98 (m, 2 H), 0.98-1.11 (m, 3 H), 1.59 (br. s., 1 H), 2.22 (br. s., 1 H), 2.48-2.65 (m, 2 H), 2.86 (d, J = 7.3 Hz, 3 H), 2.98-3.20 (m, 1 H), 5.03 (br. s., 1 H), 6.57 (td, J = 8.7, 2.3 Hz, 1 H), 6.77 (dd, J = 9.8, 2.2 Hz, 1 H), 6.84-7.00 (m, 3 H), 7.02-7.11 (m, 1 H), 7.12-7.28 (m, 2 H), 7.43 (s, 1 H). MS m/z 516 (M + H)+ 382

5-(3-fluoro-4′-(1-methyl-1H-pyrazol-4-yl)- [1,1′-biphenyl]-4-yl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.76-0.89 (m, 2 H), 1.14-1.23 (m, 2 H), 1.66-1.76 (m, 2 H), 1.76-1.87 (m, 2 H), 2.65-2.77 (m, 1 H), 2.81 (br. s., 1 H), 3.58 (br. s., 1 H), 3.78 (br. s., 2 H), 3.90 (s, 3 H), 4.01 (br. s., 2 H), 4.36 (br. s., 1 H), 7.39 (d, J = 11.5 Hz, 1 H), 7.45- 7.58 (m, 6 H), 7.61 (s, 1 H), 7.75 (s, 1 H). MS m/z 514 (M + H)+ 383

5-(4-(6-chloronaphthalen-2-yl)-2- fluorophenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.76-0.88 (m, 2 H), 1.16 (br. s., 2 H), 1.68-1.77 (m, 2 H), 1.78-1.88 (m, 2 H), 2.65-2.87 (m, 2 H), 3.57 (br. s., 1 H), 3.80 (br. s., 2 H), 3.98 (br. s., 2 H), 4.36 (br. s., 1 H), 7.37-7.53 (m, 2 H), 7.53- 7.63 (m, 2 H), 7.63-7.75 (m, 1 H), 7.75- 7.88 (m, 3 H), 7.99 (s, 1 H). MS m/z 518 (M + H)+ 384

5-(2-fluoro-4-(7-fluoronaphthalen-2- yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.82 (br s, 2 H), 1.13 (br s, 2 H), 1.72 (br, 2 H), 1.81 (br s, 2 H), 2.65-2.82 (m, 1 H), 2.95 (br s, 2 H), 3.36-4.58 (m, 6 H), 7.24 (t, J = 8.2 Hz, 1 H), 7.44-7.62 (m, 5 H), 7.80 (t, J = 6.9 Hz, 1 H), 7.88 (d, J = 8.3 Hz, 1 H), 7.94 (s, 1 H) MS m/z 502 (M + H)+ 385

6-(3-fluoro-4-(6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.45 (br. s., 2 H), 0.99 (br. s., 2 H), 1.21 (br. s., 3 H), 1.84 (br. s., 2 H), 1.92 (br. s., 2 H), 2.87 (br. s., 1 H), 3.50 (d, J = 6.2 Hz, 1 H), 3.61-4.00 (m, 3 H), 4.17 (br. s., 2 H), 7.62 (d, J = 10.7 Hz, 1 H), 7.71 (br. s., 3 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.96-8.11 (m, 2 H), 8.15 (br. s., 1 H), 8.31 (br. s., 1 H). MS m/z 507 (M + H)+ 387

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 388

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 389

6-{[(3R)-1-(Cyclopropylcarbonyl)piperidin- 3-yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 468 (M + H)+ 390

5-[5-(1-Benzofuran-5-yl)pyridin-2-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z (M + H)+ 391

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-methyl-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 392

5-[4-(1-Benzothiophen-5-yl)-3- methylphenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 393

5-[4-(1-Benzofuran-5-yl)-3-methylphenyl]- 6-{[1-(cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 394

5-[4-(1-Benzothiophen-5-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pipendin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484 (M + H)+ 395

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[(3R)- 1-(cyclopropylcarbonyl)pipendin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 396

6-{[(3R)-1-(Cyclopropylcarbonyl)pipendin- 3-yl]methyl}-5-[4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 397

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1-methyl-1H-indazol-5- yl)pyridin-2-yl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z (M + H)+ 398

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzofuran-5-yl)-2-methylphenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 399

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzofuran-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 500 (M + H)+ 400

5-[4-(6-Aminopyridin-2-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 401

Methyl 4′-(6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)biphenyl-3-carboxylate MS m/z 472 (M + H)+ 402

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[6-(1H-indol-5-yl)pyridin-3-yl]- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 404

5-[4-(1-Benzothiophen-5-yl)-3- fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 474 (M + H)+ 405

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 406

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzothiophen-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 516 (M + H)+ 407

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 494 (M + H)+ 408

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4′-hydroxybiphenyl-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 430 (M + H)+ 409

5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[(3S)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 410

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 411

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 494 (M + H)+ 412

5-(3″-Chloro-1,1′:4′,1″-terphenyl-4-yl)-6- {[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 524 (M + H)+ 413

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4″-methyl-1,1′:4′,1″- terphenyl-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 504 (M + H)+ 414

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-fluoro-4-(1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 415

5-[4-(1-Benzofuran-5-yl)-3-fluorophenyl]- 6-{[1-(cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 416

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzofuran-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 417

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzofuran-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 418

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 419

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indazol-5-yl)pyridin-2- yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 420

5-[6-(1-Benzofuran-5-yl)pyridin-3-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 455 (M + H)+ 421

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[6-(1-methyl-1H-indazol-5- yl)pyridin-3-yl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 469 (M + H)+ 422

5-[5-(1-Benzofuran-5-yl)thiophen-2-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 460 (M + H)+ 423

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indol-5-yl)thiophen-2- yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 424

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indazol-5-yl)thiophen- 2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 460 (M + H)+ 425

5-[5-(1-Benzothiophen-5-yl)thiophen-2-yl]- 6-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin- 3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 476 (M + H)+ 426

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(3H-indol-6-yl)thiophen-2- yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 427

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indazol-4-yl)thiophen- 2-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 460 (M + H)+ 428

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indol-6-yl)pyridin-2-yl]- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 429

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1H-indazol-4-yl)pyridin-2- yl]-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 430

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1-methyl-1H-indazol-5- yl)thiophen-2-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 474 (M + H)+ 431

6-{[(3S)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1H-indazol-5-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 432

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 470 (M + H)+ 433

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 488 (M + H)+ 434

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzothiophen-5-yl)-3-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 435

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1H-indol-5-yl)-3- methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 453 (M + H)+ 436

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 468 (M + H)+ 437

5-[5-(1-Benzofuran-5-yl)pyrimidin-2-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 438

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[5-(1-methyl-1H-indazol-5- yl)pyrimidin-2-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 470 (M + H)+ 439

5-[5-(1-Benzofuran-5-yl)pyrazin-2-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 440

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(1H-indol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 457 (M + H)+ 441

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 442

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(1H-indol-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 457 (M + H)+ 443

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(1H-indazol-4- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 444

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1H-indazol-5-yl)-3- methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 468 (M + H)+ 445

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1H-indazol-4-yl)-3- methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 468 (M + H)+ 446

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-methyl-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 447

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,3-dimethyl-1- benzothiophen-5-yl)-3-methylphenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 448

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1H-indazol-5-yl)-3- methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 454 (M + H)+ 449

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1H-indol-6-yl)-3- methylphenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 453 (M + H)+ 450

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 451

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4-(1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 458 (M + H)+ 452

5-[4-(2-Aminopyridin-4-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 453

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3,4-dihydro-1H-2- benzopyran-7-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 470 (M + H)+ 454

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 455

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4-quinolin-6-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 465 (M + H)+ 456

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(2,3-dihydro-1,4- benzodioxin-6-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 457

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-1,3-dihydro-2H-indol-2- one MS m/z 469 (M + H)+ 458

5-[2-(1-Benzofuran-5-yl)pyrimidin-5-yl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456 (M + H)+ 459

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[2-(1-methyl-1H-indazol-5- yl)pyrimidin-5-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 470 (M + H)+ 460

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-2- methylphenyl]-1-benzofuran-2-carbonitrile MS m/z 479 (M + H)+ 461

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-1,3-dihydro-2H-indol-2- one MS m/z 469 (M + H)+ 462

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(2,3-dihydro-1- benzofuran-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 456 (M + H)+ 463

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-2-fluorophenyl]-1-benzofuran- 2-carbonitrile MS m/z 497 (M + H)+ 464

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3,4-dihydro-2H-chromen- 6-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 470 (M + H)+ 465

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3-cyclopropyl-1-methyl- 1H-indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 466

5-[4-(3-Chloroisoquinolin-6-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 467

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]isoquinolin-1(2H)-one MS m/z 481 (M + H)+ 468

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1-methoxyisoquinolin-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 495 (M + H)+ 469

5-[4-(1-Aminoisoquinolin-6-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 480 (M + H)+ 470

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3-methoxyisoquinolin-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 495 (M + H)+  71

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3,4-dihydro-1H-2- benzopyran-6-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 470 (M + H)+ 472

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-[(1-propanoylazetidin-3- yl)methyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 456.3 (M + H)+ 473

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(2- methylpropanoyl)azetidin-3-yl]methyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 470.3 (M + H)+ 474

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-(4-quinolin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 465 (M + H)+ 475

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)phenyl]-1- benzofuran-2-carbonitrile MS m/z 465 (M + H)+ 476

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-2-methylphenyl]-1-benzofuran- 2-carbonitrile MS m/z 493 (M + H)+ 477

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-2- fluorophenyl]-1-benzofuran-2-carbonitrile MS m/z 483 (M + H)+ 478

5-[4-(6-Bromoisoquinolin-3-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 479

5-[4-(1-Chloroisoquinolin-6-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 480

6-[(1-{[1- (Hydroxymethyl)cyclopropyl]carbonyl} azetidin-3-yl)methyl]-5-[2-methyl-4-(1- methyl-1H-indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498.3 (M + H)+ 481

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-quinoxalin-6-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 452 (M + H)+ 482

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(6-pyrrolidin-1-ylpyridin-3- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 483

5-[4-(3-Amino-1-methyl-1H-indazol-6- yl)phenyl]-6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 483 (M + H)+ 484

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{4-[3-(methoxymethyl)-1- methyl-1H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 485

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{4-[3-(hydroxymethyl)-1- methyl-1H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 486

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{4-[3-(methoxymethyl)-2- methyl-2H-indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 487

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{4-[3-(hydroxymethyl)-2- methyl-2H-indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 488

N,N-Dimethyl-3-({5-[2-methyl-4-(1-methyl- 1H-indazol-5-yl)phenyl]-7-oxo-4,6- diazaspiro[2.4]hept-4-en-6- yl}methyl)azetidine-1-carboxamide MS m/z 471.3 (M + H)+ 489

6-{[1-(Cyclobutylcarbonyl)azetidin-3- yl]methyl}-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482.3 (M + H)+ 490

5-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-6- {[(3R)-1-(oxetan-3-ylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484.1 (M + H)+ 491

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,4-dimethyl-1H-indazol- 5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 492

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,7-dimethyl-1H-indazol- 5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 493

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-1-methyl-1H-indazole- 3-carbonitrile MS m/z 493 (M + H)+ 494

4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)biphenyl-3-carboxamide MS m/z 457 (M + H)+ 495

6-{[1-(2-Hydroxy-2- methylpropanoyl)azetidin-3-yl]methyl}-5- [2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 486.3 (M + H)+ 496

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-({1-[(3-methyloxetan-3- yl)carbonyl]azetidin-3-yl}methyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498.2 (M + H)+ 497

5-[4-(1H-Benzimidazol-2-yl)phenyl]-6- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 498

6-({1-[(1- Hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484.3 (M + H)+ 499

6-{[1-(Cyclopropylacetyl)azetidin-3- yl]methyl}-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482.3 (M + H)+ 500

5-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-1,2-dimethyl-1,2- dihydro-3H-indazol-3-one MS m/z 498 (M + H)+ 501

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[2-(cyclopropylmethyl)-2H- indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 494 (M + H)+ 502

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(3-fluoroisoquinolin-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 469 (M + H)+ 503

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H- pyrazolo[3,4-b]pyridin-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 504

5-[4-(1,2-Benzisoxazol-5-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 441 (M + H)+ 505

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-ethyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 506

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-ethyl-2H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 507

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-2H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 508

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indol-5-yl]phenyl}-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 481 (M + H)+ 509

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-(1H-imidazol-1- yl)pyridin-3-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 467 (M + H)+ 510

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methylquinolin-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 511

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,8-naphthyridin-2- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 512

6-[4-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-3,4-dihydroquinolin- 2(1H)-one MS m/z 483 (M + H)+ 513

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methylquinolin-7- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 514

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 480 (M + H)+ 515

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-indazol-4- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 454 (M + H)+ 516

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-{6-[1-(1-methylethyl)-1H- pyrazol-4-yl]pyridin-3-yl}phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 509 (M + H)+ 517

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-(1-methyl-1H-pyrazol-4- yl)pyridin-3-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 518

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(1,3-thiazol-2- ylcarbonyl)azetidin-3-yl]methyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 511.2 (M + H)+ 519

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-quinolin-3-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 451 (M + H)+ 520

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,7-dimethyl-1H-indazol- 5-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 521

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-ethyl-1H-indazol-5-yl)- 2-fluorophenyl]-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 486 (M + H)+ 522

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-cyclopropyl-1H-indazol- 5-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 523

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[1-(cyclopropylmethyl)-1H- indazol-5-yl]-2-fluorophenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 524

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[2-(cyclopropylmethyl)-2H- indazol-5-yl]-2-fluorophenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 525

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[1-(1- methylethyl)-1H-indol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 499 (M + H)+ 526

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[6-(1H-imidazol-1- yl)pyridin-3-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 527

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[1-(2- hydroxyethyl)-1H-indazol-5-yl]phenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 528

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(1H-indazol-3-yl)phenyl]- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 454 (M + H)+ 529

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[2-fluoro-4-(1H-indazol-3- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 530

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[3-(hydroxymethyl)-1- methyl-1H-indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 531

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-isoquinolin-3-ylphenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 451 (M + H)+ 532

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-hydroxyquinolin-3- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 467 (M + H)+ 533

3-{5-[4-(6-{[1- (Cyclopropylcarbonyl)azetidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl]-1H-indazol-1- yl}propanenitrile MS m/z 493 (M + H)+ 534

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[5-(1-methyl-1H-pyrazol-4- yl)pyridin-2-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 535

5-[4-(4-Chloro-2-methylquinolin-7- yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 536

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[2-(2- hydroxyethyl)-2H-indazol-5-yl]phenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 537

5-(4′-Chloro-2′,3-difluorobiphenyl-4-yl)-6- {[1-(cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 470 (M + H)+ 538

5-[4-(1H-Benzimidazol-2-yl)-2- fluorophenyl]-6-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 472 (M + H)+ 539

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-[1,2,4]triazolo[4,3- a]pyridin-6-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 441 (M + H)+ 540

5-[4-(2-Chloroquinolin-7-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 485 (M + H)+ 541

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1-methyl-1H-indol-6- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 453 (M + H)+ 542

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-3- yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept- 4-en-7-one MS m/z 480 (M + H)+ 543

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-(4-quinazolin-7-ylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 452 (M + H)+ 544

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4′-[1-(2-methylpropyl)-1H- pyrazol-4-yl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 545

5-[2-Methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1-(oxetan-2- ylcarbonyl)azetidin-3-yl]methyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484.2 (M + H)+ 546

6-{[1-(3-Hydroxy-2,2- dimethylpropanoyl)azetidin-3-yl]methyl}- 5-[2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 500.3 (M + H)+ 547

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3-fluoro-4′-(1-methyl-1H- pyrazol-3-yl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 548

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(2-methyl-1- benzothiophen-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 488 (M + H)+ 549

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[2-(2-hydroxyethyl)-2H- indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 550

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[1-(1-methylethyl)-1H- indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 551

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[2-(1-methylethyl)-2H- indazol-6-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 552

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-fluoro-1-(2- hydroxyethyl)-1H-indazol-5-yl]phenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 553

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[6-fluoro-2-(2- hydroxyethyl)-2H-indazol-5-yl]phenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 554

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(4-methylquinolin-7- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 555

5-[4-(2-Chloro-3-methylquinolin-7- yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 556

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[1-(2-hydroxyethyl)-1H- indazol-5-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 557

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[4-(3-methoxy-1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 558

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(2-methyl-1,3- benzothiazol-6-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 489 (M + H)+ 559

5-[4-(2-Chloro-4-methylquinolin-7- yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 499 (M + H)+ 560

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(8-fluoroquinolin-3- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 469 (M + H)+ 561

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(8-fluoro-2-methylquinolin- 7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 562

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2-methyl-1,3- benzothiazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 471 (M + H)+ 563

5-[4-(4-Chloroquinolin-7-yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 485 (M + H)+ 564

6-({1-[(1- Aminocyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 483.3 (M + H)+ 566

5-[3-Fluoro-4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 512 (M + H)+ 568

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3-(2- hydroxyethyl)-1-methyl-1H-indol-5- yl]phenyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 515 (M + H)+ 569

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,2-dimethyl-1H-indol-5- yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 570

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(2,4-dimethylquinolin-7- yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 479 (M + H)+ 571

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3′- methylbiphenyl-3- yl]cyclopropanecarboxamide MS m/z 497 (M + H)+ 572

5-[2-Fluoro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 573

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,3-dimethyl-1H-indol-5- yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 485 (M + H)+ 574

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(2-methylquinolin- 7-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 575

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(2-methylquinolin- 5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 483 (M + H)+ 576

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(2- methylquinolin-7-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 577

5-[3-Fluoro-4′-(1-methyl-1H-pyrazol-5- yl)biphenyl-4-yl]-6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 514 (M + H)+ 578

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3′- methylbiphenyl-3- yl]cyclopropanesulfonamide MS m/z 533 (M + H)+ 579

7-{3-Methyl-4-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]phenyl}quinoline-2-carboxamide MS m/z 522 (M + H)+ 580

2-Fluoro-3′-methyl-4′-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]biphenyl-4-carbonitrile MS m/z 471 (M + H)+ 581

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-{2-methyl-4-[6-(1- methylethoxy)naphthalen-2-yl]phenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 536 (M + H)+ 582

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,2-dimethyl-1H-indol-5- yl)-2-methylphenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 481 (M + H)+ 583

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5- yl)phenyl]quinoline-2-carboxylic acid MS m/z 495 (M + H)+ 584

5-[2-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 488 (M + H)+ 585

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-fluorobiphenyl-3- yl]cyclopropanecarboxamide MS m/z 515 (M + H)+ 586

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[3-(hydroxymethyl)-1- methyl-1H-indazol-5-yl]-2-methylphenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 587

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[3-(hydroxymethyl)-2- methyl-2H-indazol-5-yl]-2-methylphenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 588

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[3-(methoxymethyl)-1- methyl-1H-indazol-5-yl]-2-methylphenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 589

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{4-[3-(methoxymethyl)-2- methyl-2H-indazol-5-yl]-2-methylphenyl}- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 512 (M + H)+ 590

5-[4-(3-Chloro-1-methyl-1H-indazol-6-yl)- 2-methylphenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 502 (M + H)+ 591

5-[4-(3-Chloro-1-methyl-1H-indazol-5-yl)- 2-methylphenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 502 (M + H)+ 592

5-[4-(4-Chloro-1H-indazol-6-yl)-2- fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 492 (M + H)+ 593

1-{2-Fluoro-3′-methyl-4′-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]biphenyl-4- yl}cyclopropanecarbonitrile MS m/z 511 (M + H)+ 594

5-[4-(2-Chloroquinolin-7-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 513 (M + H)+ 595

5-[4-(7-Bromoquinolin-2-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 557 (M + H)+ 596

5-[4-(2-Chloro-3-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 527 (M + H)+ 597

5-[4-(4-Chloro-2-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 527 (M + H)+ 598

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(2-methyl-2H- indazol-4-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 599

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-4-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 600

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- indazol-3-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 601

5-{4′-[1-(Cyclopropylmethyl)-1H-pyrazol- 3-yl]-3-methylbiphenyl-4-yl}-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 548 (M + H)+ 602

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-{3-methyl-4′-[1-(2- methylpropyl)-1H-pyrazol-3-yl]biphenyl-4- yl}-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 550 (M + H)+ 603

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(2- methylquinolin-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 604

7-{3-Methyl-4-[6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]phenyl}quinoline-2-carbonitrile MS m/z 504 (M + H)+ 605

5-[4-(7-Bromo-4-methylquinolin-2-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 571 (M + H)+ 606

5-[4-(3-Chloro-1-methyl-1H-indazol-6-yl)- 2-fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 506 (M + H)+ 607

5-[4-(3-Chloro-1-methyl-1H-indazol-5-yl)- 2-fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 506 (M + H)+ 608

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3- (methoxymethyl)-1-methyl-1H-indazol-5- yl]phenyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 516 (M + H)+ 609

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{2-fluoro-4-[3- (hydroxymethyl)-1-methyl-1H-indazol-5- yl]phenyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 502 (M + H)+ 610

5-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3- methylphenyl]-2-methyl-2H-indazole-3- carbonitrile MS m/z 493 (M + H)+ 611

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5- yl)phenyl]quinoline-2-carbonitrile MS m/z 476 (M + H)+ 612

5-[3-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 488 (M + H)+ 613

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-methylbiphenyl-3- yl]cyclopropanesulfonamide MS m/z 547 (M + H)+ 614

N-[4′-(6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-methylbiphenyl-3- yl]cyclopropanecarboxamide MS m/z 511 (M + H)+ 615

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3′- fluorobiphenyl-3- yl]cyclopropanecarboxamide MS m/z 501 (M + H)+ 616

7-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3- fluorophenyl]naphthalene-2-carbonitrile MS m/z 493 (M + H)+ 617

5-[2-Fluoro-4-(7-methoxynaphthalen-2- yl)phenyl]-6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 514 (M + H)+ 618

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(7- methoxynaphthalen-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 619

N-[4′-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3′- fluorobiphenyl-3- yl]cyclopropanesulfonamide MS m/z 537 (M + H)+ 620

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-{2-methyl-4-[2- (trifluoromethyl)quinolin-7-yl]phenyl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 547 (M + H)+ 621

7-{3-Fluoro-4-[6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl]phenyl}naphthalene-2- carbonitrile MS m/z 509 (M + H)+ 622

5-[3-Chloro-4-(1-methyl-1H-indazol-5- yl)phenyl]-6-({1-[(1- hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 504 (M + H)+ 623

6-({(3R)-1-[(1- Methylcyclopropyl)carbonyl]pyrrolidin-3- yl}methyl)-5-[3-methyl-4′-(1-methyl-1H- pyrazol-5-yl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 624

5-[4-(2-Chloro-4-methylquinolin-7-yl)-2- methylphenyl]-6-({1-[(1- methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 527 (M + H)+ 627

6-({1-[(1- Methylcyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- benzimidazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 628

6-({1-[(1- Hydroxycyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-methyl-4-(1-methyl-1H- benzimidazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 484 (M + H)+ 629

5-[4-(4-Chloro-1H-indazol-6-yl)-2- methylphenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 488 (M + H)+ 630

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2′,3-difluoro-5′- (trifluoromethyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 504 (M + H)+ 631

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-{3-fluoro-3′-[(1- methylethyl)sulfonyl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 524 (M + H)+ 632

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{3-fluoro-3′-[(1- methylethyl)sulfonyl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 538 (M + H)+ 633

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-methyl-3′- (methylsulfonyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 506 (M + H)+ 634

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3-fluoro-3′- (methylsulfonyl)biphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 510 (M + H)+ 635

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(5- methoxynaphthalen-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 636

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-{3-methyl-3′-[(1- methylethyl)sulfonyl]biphenyl-4-yl}-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 534 (M + H)+ 637

6-({1-[(1- Fluorocyclopropyl)carbonyl]azetidin-3- yl}methyl)-5-[2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 490.2 (M + H)+ 638

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(5-fluoro-1,3- benzothiazol-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 493 (M + H)+ 639

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(5,6-difluoro-1,3- benzothiazol-2-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 511 (M + H)+ 640

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- methylbiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 518 (M + H)+ 641

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- fluorobiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 504 (M + H)+ 642

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- methylbiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 500 (M + H)+ 643

5-[4-(5-Chloro-1,3-benzothiazol-2-yl)-2- fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 509 (M + H)+ 644

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(2-methyl-2H- indazol-5-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 472.2 (M + H)+ 645

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- fluorobiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 490 (M + H)+ 646

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- methylbiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 532 (M + H)+ 647

6-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 536 (M + H)+ 648

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(1-methyl-1H- benzimidazol-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 472 (M + H)+ 649

5-[4-(6-Chloro-1,3-benzoxazol-2-yl)-2- fluorophenyl]-6-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 493 (M + H)+ 650

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3′-(cyclopropylsulfanyl)-3- methylbiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 651

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[3′-(cyclopropylsulfonyl)-3- fluorobiphenyl-4-yl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 652

2-[4-(6-{[1-(Cyclopropylcarbonyl)azetidin- 3-yl]methyl}-7-oxo-4,6- diazaspiro[2.4]hept-4-en-5-yl)-3- fluorophenyl]-1,3-benzothiazole-5- carbonitrile MS m/z 500 (M + H)+ 653

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[2-fluoro-4-(6-fluoro-1- methyl-1H-benzimidazol-2-yl)phenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 490 (M + H)+ 654

6-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-5-[4-(1,2-dimethyl-1H- benzimidazol-6-yl)-2-fluorophenyl]-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 486 (M + H)+ 655

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.67-0.74 (m, 2 H), 0.90-0.97 (m, 2 H), 1.41-1.56 (m, 4 H), 1.56-1.75 (m, 2 H), 1.77-1.86 (m, 0.5 H), 1.88-1.99 (m, 0.5 H), 2.07-2.18 (m, 2 H), 2.30- 2.39 (m, 0.5 H), 2.41-2.52 (m, 0.5 H), 3.00 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.20 (dd, J = 9.8, 7.9 Hz, 0.5 H), 3.29 (dt, J = 12.1, 7.7 Hz, 0.5 H), 3.46-3.55 (m, 1.5 H), 3.56-3.68 (m, 1.5 H), 3.69-3.79 (m, 1.5 H), 3.96-3.99 (m, 3 H), 3.99-4.08 (m, 4 H), 7.57-7.61 (m, 2 H), 7.61-7.69 (m, 5 H), 7.73-7.79 (m, 2 H), 7.82 (s, 1 H) MS m/z 538.3 (M + H)+ 656

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-8-oxa-1,3-diazaspiro[4.5]dec-1-en-4- one MS m/z 542.2 (M + H)+ 657

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.41-1.61 (m, 4 H), 1.77-1.93 (m, 2 H), 1.93-2.05 (m, 2 H), 2.05-2.20 (m, 3 H), 2.32-2.44 (m, 1 H), 3.02 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.08 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.28-3.39 (m, 1 H), 3.45- 3.55 (m, 1 H), 3.58-3.68 (m, 1.5 H), 3.68- 3.75 (m, 1.5 H), 3.77-3.84 (m, 1 H), 3.90 (quin, J = 7.3 Hz, 1 H), 3.99 (s, 3 H), 4.00-4.08 (m, 4 H), 4.33 (t, J = 6.6 Hz, 0.5 H), 4.40 (dd, J = 7.4, 5.9 Hz, 0.5 H), 7.56- 7.61 (m, 2 H), 7.61-7.70 (m, 5 H), 7.76 (dd, J = 8.3, 5.3 Hz, 2 H), 7.82 (s, 1 H) MS m/z 568.2 (M + H)+ 658

Methyl (3S)-3-({2-[4′-(1-methyl-1H- pyrazol-4-yl)biphenyl-4-yl]-4-oxo-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-3- yl}methyl)pyrrolidine-1-carboxylate MS m/z 528.2 (M + H)+ 659

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[(3R)-1-(trifluoroacetyl)pyrrolidin- 3-yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 566.2 (M + H)+ 660

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.38-1.58 (m, 4 H), 1.68-1.84 (m, 5 H), 2.06-2.18 (m, 2 H), 2.25-2.38 (m, 1 H), 2.98 (dd, J = 10.5, 7.3 Hz, 1 H), 3.20- 3.29 (m, 6 H), 3.32 (dd, J = 10.5, 7.0 Hz, 1 H), 3.67 (dd, J = 14.4, 7.2 Hz, 1 H), 3.73 (dd, J = 14.3, 7.8 Hz, 1 H), 3.98 (s, 3 H), 4.00-4.08 (m, 3 H), 7.59 (m, J = 8.3 Hz, 2 H), 7.62-7.70 (m, 5 H), 7.76 (d, J = 8.3 Hz, 2 H), 7.83 (s, 1 H) MS m/z 567.3 (M + H)+ 661

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.66-0.75 (m, 2 H), 0.88-0.99 (m, 2 H), 1.41-1.58 (m, 3 H), 1.58-1.65 (m, 1 H), 1.77-1.88 (m, 0.5 H), 1.91-1.99 (m, 0.5 H), 2.09-2.20 (m, 2 H), 2.37 (dt, J = 14.3, 7.4 Hz, 0.5 H), 2.48 (dt, J = 15.3, 7.5 Hz, 0.5 H), 3.02 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.23 (dd, J = 10.0, 7.7 Hz, 0.5 H), 3.30 (dt, J = 12.3, 7.8 Hz, 0.5 H), 3.45- 3.57 (m, 1.5 H), 3.58-3.70 (m, 1.5 H), 3.72-3.82 (m, 1.5 H), 3.98-4.09 (m, 4 H), 7.43-7.48 (m, 1 H), 7.70-7.77 (m, 2 H), 7.85 (dd, J = 8.3, 1.5 Hz, 1 H), 7.88- 7.99 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38 (s, 1 H), 8.95-9.01 (m, 1 H) MS m/z 509.2 (M + H)+ 662

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-(4-quinolin-7-ylphenyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.17 (dd, J = 12.8, 6.5 Hz, 3 H), 1.34- 1.52 (m, 3 H), 1.52-1.70 (m, 2 H), 1.70- 1.95 (m, 1 H), 2.01-2.14 (m, 2 H), 2.25- 2.52 (m, 1 H), 2.94-3.08 (m, 1 H), 3.19- 3.36 (m, 2 H), 3.40-3.69 (m, 3 H), 3.88- 4.03 (m, 3 H), 4.03-4.19 (m, 1 H), 7.39 (dd, J = 8.2, 4.1 Hz, 1 H), 7.62-7.69 (m, 2 H), 7.74-7.80 (m, 1 H), 7.82-7.87 (m, 2 H), 7.89 (m, J = 8.5 Hz, 1 H), 8.16 (d, J = 7.8 Hz, 1 H), 8.30 (br. s., 1 H), 8.91 (dd, J = 4.1, 1.6 Hz, 1 H) MS m/z 513.2 (M + H)+ 663

2-(4-Quinolin-7-ylphenyl)-3-({(3R)-1- [(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.43-1.63 (m, 4 H), 1.79-2.04 (m, 4 H), 2.05-2.20 (m, 3 H), 2.39 (dq, J = 18.4, 7.3 Hz, 1 H), 3.04 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.10 (dd, J = 10.8, 7.4 Hz, 0.5 H), 3.30-3.40 (m, 1 H), 3.45-3.57 (m, 1 H), 3.60-3.71 (m, 1.5 H), 3.71- 3.77 (m, 1.5 H), 3.77-3.84 (m, 1 H), 3.85- 3.95 (m, 1 H), 3.98-4.09 (m, 4 H), 4.35 (t, J = 6.6 Hz, 0.5 H), 4.37-4.43 (m, 0.5 H), 7.43-7.48 (m, 1 H), 7.68-7.78 (m, 2 H), 7.83-7.88 (m, 1 H), 7.89-7.99 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38 (s, 1 H), 8.95-9.01 (m, 1 H) MS m/z 539.2 (M + H)+ 664

Methyl (3S)-3-{[4-oxo-2-(4-quinolin-7- ylphenyl)-8-oxa-1,3-diazaspiro[4.5]dec-1- en-3-yl]methyl}pyrrolidine-1-carboxylate MS m/z 499.3 (M + H)+ 665

3-{[(3S)-1-(Pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4- quinolin-7-ylphenyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.38-1.50 (m, 1 H), 1.50-1.58 (m, 2 H), 1.70-1.85 (m, 5 H), 2.09-2.19 (m, 2 H), 2.28-2.42 (m, 1 H), 3.00 (dd, J = 10.6, 7.2 Hz, 1 H), 3.18-3.30 (m, 6 H), 3.33 (dd, J = 10.4, 7.0 Hz, 1 H), 3.69 (m, J = 14.4, 7.2 Hz, 1 H), 3.75 (dd, J = 14.7, 7.9 Hz, 1 H), 3.97-4.10 (m, 4 H), 7.46 (dd, J = 8.3, 4.2 Hz, 1 H), 7.73 (d, 2 H), 7.85 (dd, J = 8.7, 1.9 Hz, 1 H), 7.89-7.93 (m, 2 H), 7.95 (d, J = 8.3 Hz, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 8.36-8.40 (m, 1 H), 8.98 (dd, J = 4.2, 1.5 Hz, 1 H) MS m/z 538.2 (M + H)+ 666

2-(4-Quinolin-7-ylphenyl)-3-{[(3R)-1-(1,3- thiazol-2-ylcarbonyl)pyrrolidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 552.1 (M + H)+ 667

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm −0.06-0.02 (m, 3 H), 0.68-0.73 (m, 2 H), 0.86-1.00 (m, 2 H), 1.41-1.57 (m, 3 H), 1.78-1.86 (m, 0.5 H), 1.88-2.00 (m, 0.5 H), 2.07-2.20 (m, 2 H), 2.35 (m, 0.5 H), 2.47 (dt, J = 15.2, 7.3 Hz, 0.5 H), 3.01 (dd, J = 11.9, 7.0 Hz, 0.5 H), 3.21 (dd, J = 10.0, 7.7 Hz, 0.5 H), 3.29 (dt, J = 12.3, 7.8 Hz, 0.5 H), 3.44-3.56 (m, 1.5 H), 3.56-3.69 (m, 1.5 H), 3.71-3.79 (m, 1.5 H), 3.98-4.10 (m, 4 H), 6.85 (d, J = 1.5 Hz, 1 H), 7.55 (dd, J = 8.3, 1.9 Hz, 1 H), 7.61 (dd, J = 8.7, 2.3 Hz, 1 H), 7.64-7.71 (m, 3 H), 7.74-7.80 (m, 2 H), 7.84 (d, J = 1.9 Hz, 1 H) MS m/z 498.2 (M + H)+ 668

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(2-hydroxypropanoyl)pyrrolidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.13-1.35 (m, 3 H), 1.42-1.72 (m, 3 H), 1.76-2.04 (m, 1 H), 2.04-2.22 (m, 2 H), 2.29-2.43 (m, 1 H), 2.43-2.65 (m, 1 H), 3.09 (d, J = 16.1 Hz, 1 H), 3.23-3.44 (m, 2 H), 3.52-3.64 (m, 1 H), 3.64-3.80 (m, 2 H), 3.96-4.11 (m, 3 H), 4.11-4.29 (m, 1 H), 6.86 (s, 1 H), 7.49-7.74 (m, 5 H), 7.75-7.91 (m, 3 H) MS m/z 502.3 (M + H)+ 669

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.39-1.60 (m, 4 H), 1.76-1.93 (m, 2 H), 1.93-2.05 (m, 2 H), 2.05-2.18 (m, 3 H), 2.38 (dq, J = 15.5, 7.7 Hz, 1 H), 3.02 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.08 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.31-3.41 (m, 1 H), 3.42-3.57 (m, 1 H), 3.58-3.76 (m, 3 H), 3.76-3.85 (m, 1 H), 3.85-3.95 (m, 1 H), 3.98-4.11 (m, 4 H), 4.34 (dd, J = 7.2, 5.7 Hz, 0.5 H), 4.40 (dd, J = 7.6, 6.0 Hz, 0.5 H), 6.85 (s, 1 H), 7.56 (d, J = 8.7 Hz, 1 H), 7.61 (dd, J = 8.5, 3.6 Hz, 1 H), 7.63- 7.72 (m, 2 H), 7.74-7.80 (m, 2 H), 7.84 (s, 1 H) MS m/z 528.2 (M + H)+ 670

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(trifluoroacetyl)pyrrolidin-3-yl]methyl}-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 526.1 (M + H)+ 671

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)- 1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 527.2 (M + H)+ 672

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 512.2 (M + H)+ 673

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 516.3 (M + H)+ 674

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 542.2 (M + H)+ 675

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- {[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 541.2 (M + H)+ 676

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.68-0.74 (m, 2 H), 0.86-0.99 (m, 2 H), 1.38-1.54 (m, 2 H), 1.79-1.88 (m, 0.5 H), 1.89-2.00 (m, 0.5 H), 2.21-2.29 (m, 1 H), 2.30-2.53 (m, 2 H), 3.03 (ddd, J = 11.9, 7.0, 4.9 Hz, 0.5 H), 3.19-3.26 (m, 0.5 H), 3.30 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.46-3.57 (m, 1.5 H), 3.57-3.66 (m, 1 H), 3.66-3.72 (m, 0.5 H), 3.72-3.82 (m, 1.5 H), 3.97 (s, 3 H), 3.99-4.07 (m, 2 H), 4.16-4.29 (m, 2 H), 7.54-7.61 (m, 2 H), 7.64 (d, J = 8.3 Hz, 2 H), 7.66-7.70 (m, 3 H), 7.73-7.79 (m, 2 H), 7.82 (s, 1 H) MS m/z 524.3 (M + H)+ 677

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-7-oxa-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.19-1.32 (m, 3 H), 1.41-1.71 (m, 1 H), 1.91-2.01 (m, 1 H), 2.19-2.57 (m, 3 H), 3.01-3.18 (m, 1 H), 3.26-3.43 (m, 2 H), 3.60 (dd, J = 12.2, 6.9 Hz, 1 H), 3.67- 3.79 (m, 2 H), 3.98 (s, 3 H), 4.00-4.07 (m, 2 H), 4.09-4.31 (m, 3 H), 7.55-7.62 (m, 2 H), 7.62-7.71 (m, 5 H), 7.73-7.80 (m, 2 H), 7.83 (s, 1 H) MS m/z 528.3 (M + H)+ 678

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 554.3 (M + H)+ 679

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 553.2 (M + H)+ 680

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.65-0.76 (m, 2 H), 0.88-1.01 (m, 2 H), 1.41-1.56 (m, 1.5 H), 1.59-1.65 (m, 0.5 H), 1.81-1.90 (m, 0.5 H), 1.91- 2.02 (m, 0.5 H), 2.22-2.32 (m, 1 H), 2.31- 2.55 (m, 2 H), 3.04 (ddd, J = 11.9, 7.0, 4.9 Hz, 0.5 H), 3.21-3.28 (m, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.48- 3.58 (m, 1.5 H), 3.58-3.85 (m, 3 H), 3.99- 4.07 (m, 2 H), 4.15-4.29 (m, 2 H), 7.42- 7.48 (m, 1 H), 7.71-7.78 (m, 2 H), 7.85 (dd, J = 8.5, 1.7 Hz, 1 H), 7.88-7.97 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38 (s, 1 H) MS m/z 495.2 (M + H)+ 681

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-(4-quinolin-7-ylphenyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.20-1.31 (m, 3 H), 1.44-1.71 (m, 2 H), 1.83-1.93 (m, 1 H), 1.97 (dt, J = 13.4, 6.5 Hz, 1 H), 2.21-2.31 (m, 1 H), 2.33-2.59 (m, 2 H), 3.03-3.17 (m, 1 H), 3.27-3.43 (m, 2 H), 3.57-3.66 (m, 1 H), 3.68-3.80 (m, 2 H), 3.99-4.08 (m, 2 H), 4.10-4.29 (m, 3 H), 7.46 (dd, J = 8.1, 4.3 Hz, 1 H), 7.75 (dd, J = 8.5, 2.8 Hz, 2 H), 7.81-7.89 (m, 1 H), 7.90-7.94 (m, 2 H), 7.96 (d, J = 8.7 Hz, 1 H), 8.23 (d, J = 8.3 Hz, 1 H), 8.36-8.41 (m, 1 H), 8.98 (dd, J = 4.2, 1.9 Hz, 1 H) MS m/z 499.2 (M + H)+ 682

2-(4-Quinolin-7-ylphenyl)-3-({(3R)-1- [(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.38-2.22 (m, 6 H), 2.22-2.31 (m, 1 H), 2.31-2.50 (m, 2 H), 3.00-3.09 (m, 0.5 H), 3.13 (ddd, J = 10.4, 7.6, 2.5 Hz, 0.5 H), 3.30-3.43 (m, 1 H), 3.46-3.59 (m, 1 H), 3.58-3.85 (m, 4 H), 3.85-3.96 (m, 1 H), 3.97-4.09 (m, 2 H), 4.16-4.29 (m, 2 H), 4.36 (t, J = 6.0 Hz, 0.5 H), 4.38-4.44 (m, 0.5 H), 7.44-7.51 (m, 1 H), 7.70- 7.79 (m, 2 H), 7.84-7.89 (m, 1 H), 7.89- 7.95 (m, 2 H), 7.96 (dd, J = 8.5, 2.8 Hz, 1 H), 8.25 (d, J = 7.9 Hz, 1 H), 8.41 (s, 1 H), 8.93-9.01 (m, 1 H) MS m/z 525.3 (M + H)+ 683

Methyl (3S)-{[4-oxo-2-(4-quinolin-7- ylphenyl)-7-oxa-1,3-diazaspiro[4.4]non-1- en-3-yl]methyl}pyrrolidine-1-carboxylate MS m/z 458.2 (M + H)+ 684

2-(4-Quinolin-7-ylphenyl)-3-{[(3R)-1- (trifluoroacetyl)pyrrolidin-3-yl]methyl}-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 523.1 (M + H)+ 685

3-{[(3S)-1-(Pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2-(4- quinolin-7-ylphenyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 524.2 (M + H)+ 686

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.64-0.77 (m, 2 H), 0.85-1.01 (m, 2 H), 1.40-1.55 (m, 1.5 H), 1.84 (td, J = 11.7, 6.8 Hz, 0.5 H), 1.89-2.02 (m, 0.5 H), 2.21-2.30 (m, 1 H), 2.30-2.57 (m, 2 H), 3.03 (ddd, J = 12.1, 7.0, 5.1 Hz, 0.5 H), 3.23 (ddd, J = 10.1, 7.6, 6.0 Hz, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.47- 3.57 (m, 1.5 H), 3.57-3.66 (m, 1 H), 3.66- 3.73 (m, 0.5 H), 3.73-3.85 (m, 1.5 H), 3.97-4.08 (m, 2 H), 4.14-4.30 (m, 2 H), 6.85 (d, J = 1.5 Hz, 1 H), 7.53-7.58 (m, 1 H), 7.58-7.63 (m, 1 H), 7.64-7.72 (m, 3 H), 7.73-7.80 (m, 2 H), 7.84 (d, J = 1.9 Hz, 1 H) MS m/z 484.2 (M + H)+ 687

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(2-hydroxypropanoyl)pyrrolidin-3- yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.18-1.36 (m, 3 H), 1.38-1.59 (m, 1 H), 1.59-1.76 (m, 1 H), 1.81-2.07 (m, 1 H), 2.22-2.49 (m, 2 H), 2.97-3.26 (m, 3 H), 3.29-3.46 (m, 2 H), 3.62 (dd, J = 12.3, 6.5 Hz, 1 H), 3.69-3.81 (m, 2 H), 4.01-4.10 (m, 2 H), 4.18-4.30 (m, 2 H), 6.86 (d, J = 1.5 Hz, 1 H), 7.52-7.59 (m, 1 H), 7.62 (m, J = 8.5 Hz, 1 H), 7.66-7.73 (m, 3 H), 7.76-7.83 (m, 2 H), 7.83-7.88 (m, 1 H) MS m/z 488.1 (M + H)+ 688

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({(3R)- 1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.38-1.61 (m, 2 H), 1.78-2.07 (m, 4 H), 2.06-2.21 (m, 1 H), 2.21-2.30 (m, 1 H), 2.30-2.49 (m, 2 H), 3.05 (ddd, J = 12.2, 7.5, 3.0 Hz, 0.5 H), 3.08-3.15 (m, 0.5 H), 3.29-3.42 (m, 1 H), 3.46- 3.58 (m, 1 H), 3.58-3.78 (m, 3 H), 3.78- 3.85 (m, 1 H), 3.85-3.95 (m, 1 H), 3.96- 4.07 (m, 2 H), 4.13-4.28 (m, 2 H), 4.31- 4.38 (m, 0.5 H), 4.38-4.44 (m, 0.5 H), 6.85 (s, 1 H), 7.53-7.58 (m, 1 H), 7.58- 7.64 (m, 1 H), 7.64-7.73 (m, 3 H), 7.77 (dd, J = 8.3, 5.3 Hz, 2 H), 7.85 (s, 1 H) MS m/z 514.2 (M + H)+ 689

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3S)- 1-(pyrrolidin-1-ylcarbonyl)pyrrolidin-3- yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 513.2 (M + H)+ 690

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 498.2 (M + H)+ 691

3-{[(3R)-1-(2- Hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 2-[4-(1-methyl-1H-indazol-5-yl)phenyl]-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 502.3 (M + H)+ 692

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 528.2 (M + H)+ 693

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- {[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 527.2 (M + H)+ 694

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one MS m/z 524.3 (M + H)+ 695

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one MS m/z 528.2 (M + H)+ 696

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-({1-[(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 554.2 (M + H)+ 697

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[1-(pyrrolidin-1- ylcarbonyl)azetidin-3-yl]methyl}-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 553.3 (M + H)+ 698

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.63-0.73 (m, 2 H), 0.84-0.94 (m, 2 H), 1.24-1.32 (m, 1 H), 1.48-1.55 (m, 2 H), 2.07-2.18 (m, 2 H), 2.72-2.82 (m, 1 H), 3.58 (dd, J = 9.8, 5.7 Hz, 1 H), 3.87- 4.07 (m, 8 H), 4.20 (t, J = 8.3 Hz, 1 H), 7.46 (dd, J = 8.3, 4.2 Hz, 1 H), 7.72 (d, J = 8.3 Hz, 2 H), 7.85 (dd, J = 8.3, 1.9 Hz, 1 H), 7.93 (d, J = 8.7 Hz, 2 H), 7.96 (d, J = 8.3 Hz, 1 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.36- 8.40 (m, 1 H), 8.98 (dd, J = 4.2, 1.9 Hz, 1 H) MS m/z 495.2 (M + H)+ 699

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 499.2 (M + H)+ 700

2-(4-Quinolin-7-ylphenyl)-3-({1-[(2R)- tetrahydro-furan-2-ylcarbonyl]azetidin-3- yl}methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.51 (d, J = 13.2 Hz, 2 H), 1.77-1.91 (m, 2 H), 1.98-2.18 (m, 4 H), 2.71-2.80 (m, 1 H), 3.57-3.64 (m, 1 H), 3.72-3.85 (m, 2 H), 3.86-4.06 (m, 8 H), 4.18-4.37 (m, 2 H), 7.46 (dd, J = 8.3, 4.2 Hz, 1 H), 7.72 (dd, J = 8.3, 4.5 Hz, 2 H), 7.85 (d, J = 8.3 Hz, 1 H), 7.92 (d, 2 H), 7.96 (d, J = 8.3 Hz, 1 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.38 (s, 1 H), 8.98 (dd, J = 4.2, 1.5 Hz, 1 H) MS m/z 525.2 (M + H)+ 701

3-{[1-(Pyrrolidin-1-ylcarbonyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 524.2 (M + H)+ 702

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 484.2 (M + H)+ 703

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(2- hydroxypropanoyl)azetidin-3-yl]methyl}-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 488.2 (M + H)+ 704

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({1- [(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 514.2 (M + H)+ 705

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (pyrrolidin-1-ylcarbonyl)azetidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 513.2 (M + H)+ 706

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.70 (dd, J = 7.9, 3.1 Hz, 2 H), 0.85- 0.94 (m, 2 H), 1.22-1.33 (m, 1 H), 1.51 (d, J = 13.6 Hz, 2 H), 2.12 (ddd, J = 13.7, 9.0, 5.4 Hz, 2 H), 2.70-2.83 (m, 1 H), 3.57 (dd, J = 9.7, 5.6 Hz, 1 H), 3.85-3.93 (m, 2 H), 3.93-4.00 (m, 2 H), 4.00-4.07 (m, 4 H), 4.14 (s, 3 H), 4.20 (t, J = 8.8 Hz, 1 H), 7.52 (d, J = 8.8 Hz, 1 H), 7.63-7.71 (m, 3 H), 7.80 (d, J = 8.3 Hz, 2 H), 7.95- 8.00 (m, 1 H), 8.07 (d, J = 1.0 Hz, 1 H) MS m/z 498.2 (M + H)+ 707

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one MS m/z 502.2 (M + H)+ 708

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({1-[(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 528.2 (M + H)+ 709

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- {[1-(pyrrolidin-1-ylcarbonyl)azetidin-3- yl]methyl}-8-oxa-1,3-diazaspiro[4.5]dec-1- en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.46-1.55 (m, 2 H), 1.76 (dt, J = 6.5, 3.5 Hz, 4 H), 2.12 (ddd, J = 13.7, 8.8, 5.5 Hz, 2 H), 2.59-2.72 (m, 1 H), 3.17-3.25 (m, 4 H), 3.54 (dd, J = 8.2, 5.6 Hz, 2 H), 3.85-3.94 (m, 4 H), 4.00-4.07 (m, 4 H), 4.14 (s, 3 H), 7.51 (d, J = 8.8 Hz, 1 H), 7.63-7.71 (m, 3 H), 7.79 (d, J = 8.3 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s, 1 H) MS m/z 527.3 (M + H)+ 710

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 510.3 (M + H)+ 711

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 514.2 (M + H)+ 712

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-({1-[(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 540.2 (M + H)+ 713

2-[4′-(1-Methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-3-{[1-(pyrrolidin-1- ylcarbonyl)azetidin-3-yl]methyl}-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 539.2 (M + H)+ 714

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 481.2 (M + H)+ 715

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.16-1.30 (m, 3 H), 2.26 (dt, J = 12.4, 6.0 Hz, 1 H), 2.37-2.50 (m, 1 H), 2.78-2.96 (m, 1 H), 3.61-3.70 (m, 0.5 H), 3.73 (dd, J = 10.5, 5.5 Hz, 0.5 H), 3.78- 3.86 (m, 0.5 H), 3.86-4.06 (m, 6 H), 4.06-4.18 (m, 2.5 H), 4.18-4.29 (m, 2.5 H), 7.48 (dd, J = 8.3, 4.3 Hz, 1 H), 7.69- 7.78 (m, 2 H), 7.82-7.90 (m, 1 H), 7.90- 8.01 (m, 3 H), 8.24 (d, J = 8.3 Hz, 1 H), 8.40 (br. s., 1 H), 8.99 (dd, J = 4.3, 1.5 Hz, 1 H) MS m/z 485.2 (M + H)+ 716

2-(4-Quinolin-7-ylphenyl)-3-({1-[(2R)- tetrahydro-furan-2-ylcarbonyl]azetidin-3- yl}methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 511.3 (M + H)+ 717

3-{[1-(Pyrrolidin-1-ylcarbonyl)azetidin-3- yl]methyl}-2-(4-quinolin-7-ylphenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 510.2 (M + H)+ 718

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 470.2 (M + H)+ 719

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1-(2- hydroxypropanoyl)azetidin-3-yl]methyl}-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 474.1 (M + H)+ 720

2-[4-(1-Benzofuran-5-yl)phenyl]-3-({1- [(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 500.2 (M + H)+ 721

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (pyrrolidin-1-ylcarbonyl)azetidin-3- yl]methyl}-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 499.3 (M + H)+ 722

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 484.3 (M + H)+ 723

3-{[1-(2-Hydroxypropanoyl)azetidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 488.2 (M + H)+ 724

2-[4-(1-Methyl-1H-indazol-5-yl)phenyl]-3- ({1-[(2R)-tetrahydro-furan-2- ylcarbonyl]azetidin-3-yl}methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 514.2 (M + H)+ 725

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-6-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxo-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.65-0.76 (m, 2 H), 0.85-1.00 (m, 2 H), 1.39-1.55 (m, 1.5 H), 1.79-1.90 (m, 0.5 H), 1.96 (td, J = 12.3, 6.8 Hz, 0.5 H), 2.37 (br. s., 0.5 H), 2.44-2.55 (m, 0.5 H), 3.02 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.21- 3.27 (m, 0.5 H), 3.31 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.46-3.58 (m, 1.5 H), 3.58-3.82 (m, 6 H), 3.97 (s, 3 H), 4.28-4.33 (m, 2 H), 4.33-4.38 (m, 2 H), 7.56-7.61 (m, 2 H), 7.62-7.66 (m, 2 H), 7.66-7.71 (m, 3 H), 7.74-7.80 (m, 2 H), 7.82 (s, 1 H) MS m/z 567.3 (M + H)+ 726

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 6-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl- 4-yl]-8-oxo-2,5,7-triazaspiro[3.4]oct-5- ene-2-carboxylate ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.26 (t, J = 6.9 Hz, 3 H), 1.39-1.56 (m, 1 H), 1.59-1.73 (m, 1.5 H), 1.83- 2.04 (m, 1.5 H), 2.32-2.47 (m, 0.5 H), 2.48-2.60 (m, 0.5 H), 3.00-3.18 (m, 1 H), 3.28-3.44 (m, 2 H), 3.54-3.66 (m, 1 H), 3.68-3.79 (m, 5 H), 3.98 (s, 3 H), 4.08-4.24 (m, 1 H), 4.29-4.40 (m, 4 H), 7.57-7.62 (m, 2 H), 7.62-7.72 (m, 5 H), 7.75-7.81 (m, 2 H), 7.83 (s, 1 H) MS m/z 571.3 (M + H)+ 727

Methyl 6-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-oxo-7-({(3R)-1-[(2R)- tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3- yl}methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.38-1.61 (m, 1.5 H), 1.78-2.24 (m, 5.5 H), 2.42 (m, 1 H), 3.04 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.13 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.37 (dq, J = 11.3, 7.8 Hz, 1 H), 3.46-3.58 (m, 1 H), 3.59-3.77 (m, 6 H), 3.78-3.84 (m, 1 H), 3.84-3.94 (m, 1 H), 3.98 (s, 3 H), 4.27-4.38 (m, 4.5 H), 4.38-4.43 (m, 0.5 H), 7.56-7.62 (m, 2 H), 7.62-7.72 (m, 5 H), 7.75-7.80 (m, 2 H), 7.80-7.84 (m, 1 H) MS m/z 597.4 (M + H)+ 728

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-oxo-6-(4-quinolin-7- ylphenyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.60-0.77 (m, 2 H), 0.84-1.01 (m, 2 H), 1.36-1.56 (m, 2 H), 1.79-1.92 (m, 0.5 H), 1.92-2.03 (m, 0.5 H), 2.30-2.46 (m, 0.5 H), 2.51 (m, 0.5 H), 3.04 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.22-3.29 (m, 1 H), 3.29-3.36 (m, 0.5 H), 3.48-3.59 (m, 1.5 H), 3.59-3.85 (m, 6 H), 4.25-4.42 (m, 4 H), 7.41-7.50 (m, 1 H), 7.76 (t, J = 8.3 Hz, 2 H), 7.85 (dd, J = 8.7, 1.9 Hz, 1 H), 7.88-8.00 (m, 3 H), 8.21 (d, J = 7.9 Hz, 1 H), 8.37 (s, 1 H), 8.90-9.01 (m, 1 H) MS m/z 538.2 (M + H)+ 729

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 8-oxo-6-(4-quinolin-7-ylphenyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.17-1.31 (m, 3 H), 1.45-1.57 (m, 1 H), 1.90 (m, 0.5 H), 1.98 (m, 0.5 H), 2.31-2.48 (m, 0.5 H), 2.49-2.61 (m, 0.5 H), 3.07 (dd, J = 12.3, 6.2 Hz, 0.5 H), 3.11- 3.19 (m, 0.5 H), 3.27-3.44 (m, 2 H), 3.57-3.65 (m, 1 H), 3.67-3.79 (m, 2 H), 3.74 (s, 3 H), 4.14 (q, J = 6.3 Hz, 0.5 H), 4.20 (q, J = 6.5 Hz, 0.5 H), 4.28-4.41 (m, 4 H), 7.46 (dd, J = 12.5, 4.2 Hz, 1 H), 7.75 (dd, J = 8.3, 3.4 Hz, 2 H), 7.80-7.89 (m, 1 H), 7.87-7.99 (m, 3 H), 8.23 (d, J = 8.3 Hz, 1 H), 8.39 (d, J = 4.9 Hz, 1 H), 8.92- 9.04 (m, 1 H) MS m/z 542.3 (M + H)+ 730

Methyl 8-oxo-6-(4-quinolin-7-ylphenyl)-7- ({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.41-1.56 (m, 1 H), 1.78-1.90 (m, 1.5 H), 1.90-2.07 (m, 2.5 H), 2.07-2.15 (m, 0.5 H), 2.15-2.23 (m, 0.5 H), 2.44 (m, 1 H), 3.06 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.15 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.29- 3.44 (m, 1 H), 3.47-3.59 (m, 1 H), 3.60- 3.86 (m, 4 H), 3.73 (s, 3 H), 3.85-3.95 (m, 1 H), 4.28-4.39 (m, 4 H), 4.38-4.44 (m, 1 H), 7.42-7.51 (m, 1 H), 7.76 (dd, J = 12.5, 8.3 Hz, 2 H), 7.86 (d, J = 8.3 Hz, 1 H), 7.89-8.01 (m, 3 H), 8.22 (d, J = 8.3 Hz, 1 H), 8.36 (s, 1 H), 8.93-9.04 (m, 1 H) MS m/z 568.3 (M + H)+ 731

Methyl 8-oxo-6-(4-quinolin-7-ylphenyl)-7- {[(3R)-1-(trifluoroacetyl)pyrrolidin-3- yl]methyl}-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 566.1 (M + H)+ 732

Methyl 8-oxo-7-{[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-6-(4- quinolin-7-ylphenyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 567.2 (M + H)+ 733

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-7- {[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.72 (m, 2 H), 0.86-1.01 (m, 2 H), 1.39-1.55 (m, 1.5 H), 1.64 (m, 1 H), 1.81- 1.91 (m, 0.5 H), 1.92-2.04 (m, 0.5 H), 2.38 (br. s., 0.5 H), 2.44-2.56 (m, 0.5 H), 3.02 (dd, J = 11.9, 7.0 Hz, 0.5 H), 3.25 (dd, J = 10.0, 7.7 Hz, 0.5 H), 3.32 (dt, J = 12.1, 7.9 Hz, 0.5 H), 3.48-3.57 (m, 1.5 H), 3.58-3.72 (m, 1.5 H), 3.73 (s, 3 H), 3.74- 3.81 (m, 1 H), 4.26-4.39 (m, 4 H), 6.85 (d, J = 2.3 Hz, 1 H), 7.56 (dd, J = 8.3, 1.9 Hz, 1 H), 7.57-7.64 (m, 1 H), 7.65-7.73 (m, 3 H), 7.74-7.82 (m, 2 H), 7.85 (d, J = 1.5 Hz, 1 H) MS m/z 527.3 (M + H)+ 734

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-7- {[(3R)-1-(2-hydroxypropanoyl)pyrrolidin-3- yl]methyl}-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z 531.2 (M + H)+ 735

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-8- oxo-7-({(3R)-1-[(2R)-tetrahydro-furan-2- ylcarbonyl]pyrrolidin-3-yl}methyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.42-1.55 (m, 0.5 H), 1.78-2.07 (m, 4 H), 2.06-2.23 (m, 1 H), 2.31-2.50 (m, 1 H), 3.04 (dd, J = 12.5, 7.2 Hz, 0.5 H), 3.13 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.30- 3.41 (m, 1 H), 3.47-3.58 (m, 1 H), 3.60- 3.69 (m, 1 H), 3.68-3.77 (m, 4.5 H), 3.81 (q, J = 6.7 Hz, 1 H), 3.84-3.94 (m, 1 H), 4.27-4.38 (m, 4 H), 4.38-4.43 (m, 0.5 H), 6.82-6.87 (m, 1 H), 7.54-7.59 (m, 1 H), 7.61 (dd, J = 8.7, 3.8 Hz, 1 H), 7.63- 7.73 (m, 3 H), 7.78 (dd, J = 8.3, 6.0 Hz, 2 H), 7.85 (s, 1 H) MS m/z 557.2 (M + H)+ 736

Methyl 6-[4-(1-benzofuran-5-yl)phenyl]-8- oxo-7-{[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 556.2 (M + H)+ 737

Methyl 7-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-6-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 0.63-0.77 (m, 2 H), 0.87-1.01 (m, 2 H), 1.41-1.55 (m, 1.5 H), 1.80-1.91 (m, 0.5 H), 1.92-2.02 (m, 0.5 H), 2.38 (br. s., 0.5 H), 2.43-2.57 (m, 0.5 H), 3.02 (dd, J = 12.1, 7.2 Hz, 0.5 H), 3.25 (t, J = 8.9 Hz, 0.5 H), 3.32 (m, 0.5 H), 3.49-3.57 (m, 1.5 H), 3.60-3.80 (m, 6 H), 4.13 (s, 3 H), 4.29-4.34 (m, 2 H), 4.34-4.38 (m, 2 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.66-7.73 (m, 3 H), 7.77-7.83 (m, 2 H), 7.98 (s, 1 H), 8.06 (s, 1 H) MS m/z 541.3 (M + H)+ 738

Methyl 7-{[(3R)-1-(2- hydroxypropanoyl)pyrrolidin-3-yl]methyl}- 6-[4-(1-methyl-1H-indazol-5-yl)phenyl]-8- oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 545.2 (M + H)+ 739

Methyl 6-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxo-7-({(3R)-1-[(2R)- tetrahydro-furan-2-ylcarbonyl]pyrrolidin-3- yl}methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate ¹H NMR (600 MHz, CHLOROFORM-d) δ ppm 1.44-1.54 (m, 1 H), 1.79-2.22 (m, 5.5 H), 2.32-2.52 (m, 1 H), 3.04 (dd, J = 12.3, 7.4 Hz, 0.5 H), 3.14 (dd, J = 10.6, 7.2 Hz, 0.5 H), 3.31-3.41 (m, 1 H), 3.48- 3.58 (m, 1 H), 3.59-3.78 (m, 6.5 H), 3.78- 3.84 (m, 1 H), 3.84-3.95 (m, 1 H), 4.10- 4.15 (m, 3 H), 4.29-4.38 (m, 4.5 H), 4.38-4.44 (m, 0.5 H), 7.51 (dd, J = 8.7, 3.4 Hz, 1 H), 7.66-7.73 (m, 3 H), 7.77- 7.83 (m, 2 H), 7.98 (s, 1 H), 8.05-8.08 (m, 1 H) MS m/z 571.2 (M + H)+ 740

Methyl 6-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-oxo-7-{[(3S)-1-(pyrrolidin-1- ylcarbonyl)pyrrolidin-3-yl]methyl}-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 570.2 (M + H)+ 741

8-Acryloyl-2-[4-(1-benzofuran-6- yl)phenyl]-3-{[(3R)-1- (cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-1,3,8-triazaspiro[4.5]dec-1-en- 4-one ¹H NMR (400 MHz, CDCl₃) d 0.71-0.72 (m, 2 H), 0.88-0.98 (m, 3 H), 1.44-1.65 (m, 5 H), 2.30-2.48 (m, 2 H), 3.01-3.31 (m, 2 H), 3.50-3.79 (m, 6 H), 4.00-4.07 (m, 1 H), 4.50-4.59 (m, 1 H), 5.72 (d, J = 10.6 Hz, 1 H), 6.34 (m, 1 H), 6.63 (dd, J = 10.6, 16.7 Hz, 1 H), 6.85 (d, J = 1.5 Hz, 1 H), 7.54-7.70 (m, 5 H), 7.76-7.80 (m, 2 H), 7.84 (s, 1 H) MS m/z 551.2 (M + H)+ 742

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(2,3-dimethyl-1- benzothiophen-5-yl)phenyl]-8-(2- hydroxyethyl)-1,3,8-triazaspiro[4.5]dec-1- en-4-one ¹H NMR (300 MHz, CDCl₃) d ppm 0.61- 0.87 (m, 5 H), 1.40-1.57 (m, 4 H), 1.75- 2.10 (m, 4 H), 2.30 (s, 3 H), 2.45 (s, 3 H), 2.61 (t, J = 5.0 Hz, 1H), 2.68-2.75 (m, 1 H), 2.85-2.97 (m, 3 H), 3.10-3.25 (m, 1 H), 3.39-3.70 (m, 8 H), 7.45 (dd, J = 1.4, 8.2 Hz, 1H), 7.59 (dd, J = 2.7, 8.2 Hz, 2 H), 7.72-7.77 (m, 4 H) MS m/z 585 (M + H)+ 743

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CDCl3) d ppm 0.61- 0.87 (m, 5 H), 1.40-1.57 (m, 4 H), 1.75- 2.10 (m, 4 H), 2.30 (s, 3 H), 2.45 (s, 3 H), 2.61 (t, J = 5.0 Hz, 1H), 2.68-2.75 (m, 1 H), 2.85-2.97 (m, 3 H), 3.10-3.25 (m, 1 H), 3.39-3.70 (m, 8 H), 7.45 (dd, J = 1.4, 8.2 Hz, 1H), 7.59 (dd, J = 2.7, 8.2 Hz, 2 H), 7.72-7.77 (m, 4 H) MS m/z 539 (M + H)+ 744

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (1-methylethyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CDCl3) d ppm 0.6-1.0 (m, 5 H), 1.05-1.20 (m, 6 H), 1.25-3.60 (m, 18 H), 6.58 (s, 1 H), 7.47 (s, 1 H), 7.51-7.60 (m, 2 H), 7.78-7.82 (m, 2 H), 7.91 (d, J = 7.0 Hz, 2 H), 7.99 (s, 1 H), 11.28 (s, 1 H) MS m/z 538 (M + H)+ 745

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.55-0.65 (m, 4 H), 1.35-2.40 (m, 7 H), 2.85-3.71 (m, 10 H), 2.96 (s, 3 H), 6.53 (s, 1 H), 7.41 (t, J = 2.6 Hz, 1 H), 7.48-7.54 (m, 2 H), 7.75-7.79 (m, 2 H), 7.86-7.88 (m, 2 H), 7.94 (s, 1 H), 11.21 (s, 1 H) MS m/z 574 (M + H)+ 746

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.65 (m, 4 H), 1.20-2.35 (m, 7 H), 2.79-3.65 (m, 10 H), 2.92 (s, 3 H), 7.01 (d, J = 1.9 Hz, 1 H), 7.64-7.71 (m, 2 H), 7.75-7.78 (m, 2 H), 7.84-7.88 (m, 2 H), 8.00-8.03 (m, 2 H) MS m/z 575 (M + H)+ 747

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.62-0.67 (m, 4 H), 1.32-1.95 (m, 7 H), 2.15-2.38 (m , 1 H), 2.52-2.60 (m, 3 H), 2.83-2.89 (m, 3 H), 3.07-3.15 (m, 2 H), 3.32 (s, 3 H), 3.45-3.70 (m, 6 H), 6.53 (s, 1 H), 7.41 (t, J = 2.6 Hz, 1 H), 7.46-7.54 (m, 2 H), 7.73-7.77 (m, 2 H), 7.84-7.87 (m, 2 H), 7.94 (s, 1 H), 11.22 (s, 1 H) MS m/z 554 (M + H)+ 748

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.60-0.67 (m, 4 H), 1.35-1.95 (m, 7 H), 2.15-2.35 (m, 1 H), 2.50-2.60 (m, 3 H), 2.80-2.90 (m, 3 H), 3.05-3.15 (m, 2 H), 3.26 (s, 3 H), 3.45-3.69 (m, 6 H), 7.66- 7.69 (m, 1 H), 7.75-7.80 (m, 3 H), 7.88- 7.91 (m, 2 H), 8.16 (d, J = 5.2 Hz, 2 H), 13.18 (s, 1 H) MS m/z 555 (M + H)+ 749

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[(3R)- 1-(cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.65-0.70 (m, 4 H), 1.42-2.0 (m, 7 H), 2.20-2.45 (m, 1 H), 2.55-2.65 (m, 3 H), 2.85-2.92 (m, 3 H), 3.10-3.35 (m, 2 H), 3.31 (s, 3 H), 3.48-3.65 (m, 4 H), 3.69- 3.74 (m, 2 H), 7.10 (d, J = 1.7 Hz, 1 H), 7.75-7.86 (m, 4 H), 7.92-7.95 (m, 2 H), 8.09-8.13 (m, 2 H) MS m/z 555 (M + H)+ 750

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-8-(2-methoxyethyl)-2-[4-(1- methyl-1H-indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.54-0.70 (m, 4 H), 1.26-1.99 (m, 7 H), 2.11-2.38 (m, 1 H), 2.56 (t, J = 5.9 Hz, 3 H), 2.75-2.91 (m, 2.5 H), 3.02-3.17 (m, 1 H), 3.17-3.24 (m, 0.5 H), 3.25 (s, 3 H), 3.35-3.59 (m, 4 H), 3.65 (t, J = 7.2 Hz, 2 H), 4.09 (s, 3 H), 7.72-7.85 (m, 4 H), 7.85-7.94 (m, 2 H), 8.13 (s, 2 H) MS m/z 569 (M + H)+ 751

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.52-0.71 (m, 4 H), 1.26-1.97 (m, 7 H), 2.12-2.42 (m, 1 H), 2.87 (dd, J = 11.3, 6.6 Hz, 0.5 H), 3.03-3.18 (m, 1 H), 3.19- 3.29 (m, 1 H), 3.38-3.56 (m, 2.5 H), 3.63- 3.81 (m, 3 H), 3.95 (d, J = 13.9 Hz, 1 H), 4.29 (d, J = 13.2 Hz, 1 H), 6.52 (br. s., 1 H), 7.40 (t, J = 2.5 Hz, 1 H), 7.44-7.56 (m, 2 H), 7.72-7.83 (m, 2 H), 7.83-7.91 (m, 2 H), 7.94 (s, 1 H), 11.21 (br. s., 1 H) MS m/z 592 (M + H)+ 752

3-{[(3R)-1- (Cyclopropylcarbonyl)pyrrolidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-(trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.63 (d, J = 5.4 Hz, 4 H), 1.28-1.98 (m, 7 H), 2.12-2.40 (m, 1 H), 2.86 (dd, J = 11.5, 6.7 Hz, 0.5 H), 3.01-3.18 (m, 1 H), 3.19- 3.29 (m, 1 H), 3.38-3.52 (m, 2.5 H), 3.63- 3.80 (m, 3 H), 3.95 (d, J = 13.9 Hz, 1 H), 4.09 (s, 3 H), 4.29 (d, J = 13.7 Hz, 1 H), 7.73-7.87 (m, 4 H), 7.92 (dd, J = 8.2, 2.1 Hz, 2 H), 8.14 (d, J = 4.1 Hz, 2 H) MS m/z 607 (M + H)+ 753

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.76 (m, 2 H), 0.91 (br. s., 2 H), 1.18 (t, J = 7.8 Hz, 6 H), 1.22-1.36 (m, 1 H), 1.49-1.67 (m, 2 H), 1.86-2.10 (m, 2 H), 2.76 (br. s., 1 H), 2.80-2.97 (m, 1 H), 3.37-3.52 (m, 1 H), 3.59 (dd, J = 9.6, 5.6 Hz, 1 H), 3.73 (t, J = 11.3 Hz, 1 H), 3.80-4.07 (m, 5 H), 4.19 (t, J = 8.1 Hz, 1 H), 4.51 (d, J = 13.2 Hz, 1 H), 6.56-6.70 (m, 1 H), 7.27-7.35 (m, 1 H), 7.42-7.56 (m, 2 H), 7.63 (d, J = 8.2 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 2 H), 7.91 (s, 1 H), 8.55 (br. s., 1 H) MS m/z 552 (M + H)+ 754

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (2-methylpropanoyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.77 (m, 2 H), 0.86-0.99 (m, 2 H), 1.18 (t, J = 7.8 Hz, 6 H), 1.23-1.31 (m, 1 H), 1.50-1.80 (m, 4 H), 1.88-2.09 (m, 2 H), 2.80 (br. s., 1 H), 2.82-2.95 (m, 1 H), 3.35-3.51 (m, 1 H), 3.57 (dd, J = 9.5, 5.6 Hz, 1 H), 3.63-3.82 (m, 1 H), 3.82-4.07 (m, 4 H), 4.21 (t, J = 8.2 Hz, 1 H), 4.51 (d, J = 13.3 Hz, 1 H), 7.52-7.62 (m, 1 H), 7.66 (d, J = 7.8 Hz, 3 H), 7.79 (d, J = 8.0 Hz, 2 H), 8.00 (s, 1 H), 8.17 (br. s., 1 H) MS m/z 553 (M + H)+ 755

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.77 (m, 2 H), 0.79-0.98 (m, 2 H), 1.22-1.35 (m, 1 H), 1.59 (d, J = 12.8 Hz, 2 H), 2.05-2.27 (m, 3 H), 2.60-2.84 (m, 5 H), 2.96 (d, J = 11.3 Hz, 2 H), 3.39 (s, 3 H), 3.58 (t, J = 5.4 Hz, 2 H), 3.76- 4.03 (m, 4 H), 4.17 (t, J = 8.0 Hz, 1 H), 6.64 (br. s., 1 H), 7.28-7.36 (m, 1 H), 7.41-7.55 (m, 2 H), 7.61 (d, J = 8.1 Hz, 2 H), 7.79 (d, J = 8.1 Hz, 2 H), 7.90 (s, 1 H), 8.44 (br. s., 1 H) MS m/z 540 (M + H)+ 756

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (2-methoxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61-0.75 (m, 2 H), 0.85-0.94 (m, 2 H), 1.25-1.33 (m, 1 H), 1.59 (d, J = 13.2 Hz, 2 H), 2.07-2.25 (m, 2 H), 2.62-2.84 (m, 5 H), 2.91-3.03 (m, 2 H), 3.39 (s, 3 H), 3.55-3.62 (m, 2 H), 3.78-4.05 (m, 4 H), 4.19 (t, J = 8.2 Hz, 1 H), 7.58 (m, J = 8.8 Hz, 1 H), 7.61-7.68 (m, 3 H), 7.71-7.86 (m, 2 H), 7.99 (s, 1 H), 8.16 (s, 1 H), 10.56 (br. s., 1 H) MS m/z 541 (M + H)+ 757

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1H- indol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.69 (dd, J = 7.5, 3.0 Hz, 2 H), 0.84- 0.95 (m, 2 H), 1.60 (d, J = 12.8 Hz, 2 H), 1.98-2.23 (m, 3 H), 2.68 (t, J = 5.1 Hz, 2 H), 2.72-2.86 (m, 3 H), 2.94 (d, J = 11.5 Hz, 2 H), 3.54-3.62 (m, 1 H), 3.62-3.73 (m, 2 H), 3.77-4.04 (m, 4 H), 4.18 (t, J = 8.1 Hz, 1 H), 6.65 (br. s., 1 H), 7.29 (br. s., 1 H), 7.41-7.58 (m, 2 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.80 (d, J = 8.1 Hz, 2 H), 7.91 (s, 1 H), 8.34 (br. s., 1 H) MS m/z 526 (M + H)+ 758

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-hydroxyethyl)-2-[4-(1H- indazol-5-yl)phenyl]-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.77 (m, 2 H), 0.87-0.96 (m, 2 H), 1.25-1.32 (m, 2 H), 1.61 (d, J = 13.2 Hz, 2 H), 2.04-2.16 (m, 2 H), 2.69 (t, J = 5.2 Hz, 2 H), 2.73-2.86 (m, 3 H), 2.88- 3.00 (m, 2 H), 3.54-3.62 (m, 1 H), 3.67 (t, J = 5.2 Hz, 2 H), 3.78-4.04 (m, 4 H), 4.20 (t, J = 8.1 Hz, 1 H), 7.59 (m, J = 8.7 Hz, 1 H), 7.63-7.71 (m, 3 H), 7.78 (d, J = 8.1 Hz, 2 H), 8.00 (s, 1 H), 8.16 (s, 1 H) MS m/z 527 (M + H)+ 759

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.63-0.75 (m, 2 H), 0.85-0.95 (m, 2 H), 1.19-1.34 (m, 1 H), 1.54 (d, J = 13.3 Hz, 2 H), 1.87-2.03 (m, 2 H), 2.60-2.83 (m, 1 H), 3.09-3.29 (m, 4 H), 3.56 (dd, J = 9.7, 5.7 Hz, 1 H), 3.80-3.97 (m, 4 H), 3.98 (s, 3 H), 4.18 (t, J = 8.4 Hz, 1 H), 7.56- 7.70 (m, 7 H), 7.77 (d, J = 8.2 Hz, 2 H), 7.83 (s, 1 H) MS m/z 523 (M + H)+ 760

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.59-0.78 (m, 2 H), 0.90 (br. s., 2 H), 1.72 (br. s., 1 H), 2.16 (t, J = 10.0 Hz, 2 H), 2.66-2.81 (m, 1 H), 2.85 (s, 3 H), 3.31-3.43 (m, 2 H), 3.54-3.64 (m, 1 H), 3.67-4.07 (m, 7 H), 4.20 (t, J = 7.6 Hz, 1 H), 6.86 (br. s., 1 H), 7.52-7.73 (m, 5 H), 7.75-7.92 (m, 3 H) MS m/z 561 (M + H)+ 761

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1-methyl-1H-indazol-5- yl)phenyl]-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.61-0.77 (m, 2 H), 0.90 (br. s., 2 H), 1.14-1.36 (m, 2 H), 2.06-2.25 (m, 2 H), 2.67-2.80 (m, 1 H), 2.85 (s, 3 H), 3.29-3.63 (m, 3 H), 3.80 (d, J = 11.7 Hz, 2 H), 3.86-4.05 (m, 4 H), 4.13 (s, 3 H), 4.16-4.26 (m, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.66 (t, J = 8.7 Hz, 3 H), 7.81 (d, J = 8.0 Hz, 2 H), 7.97 (s, 1 H), 8.07 (s, 1 H) MS m/z 575 (M + H)+ 762

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.47-0.73 (m, 4 H), 1.30-1.45 (m, 1 H), 1.62 (d, J = 12.8 Hz, 2 H), 1.91 (t, J = 10.3 Hz, 2 H), 2.56-2.71 (m, 1 H), 2.95 (s, 3 H), 3.21 (t, J = 10.3 Hz, 2 H), 3.61 (d, J = 11.5 Hz, 2 H), 3.67-3.82 (m, 2 H), 3.88 (d, J = 7.3 Hz, 2 H), 4.15 (t, J = 8.3 Hz, 1 H), 6.52 (br. s., 1 H), 7.41 (br. s., 1 H), 7.44-7.58 (m, 2 H), 7.74 (d, J = 8.1 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.94 (s, 1 H) MS m/z 560 (M + H)+ 763

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (methylsulfonyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.51-0.70 (m, 4 H), 1.29-1.45 (m, 1 H), 1.64 (d, J = 13.2 Hz, 2 H), 1.92 (t, J = 10.4 Hz, 2 H), 2.57-2.70 (m, 1 H), 2.95 (s, 3 H), 3.19-3.27 (m, 2 H), 3.54-3.68 (m, 2 H), 3.68-3.82 (m, 2.5 H), 3.88 (d, J = 7.1 Hz, 2.5 H), 4.15 (t, J = 8.0 Hz, 1 H), 7.63- 7.70 (m, 1 H), 7.71-7.83 (m, 3 H), 7.91 (d, J = 8.2 Hz, 2 H), 8.16 (br. s., 2 H), 13.18 (br. s., 1 H) MS m/z 561 (M + H)+ 764

2-[4-(1-Benzofuran-5-yl)phenyl]-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.58-0.77 (m, 2 H), 0.91 (br. s., 2 H), 1.26 (br. s., 3 H), 1.96-2.16 (m, 2 H), 2.64-2.88 (m, 1 H), 3.53-3.70 (m, 2 H), 3.71-4.12 (m, 6 H), 4.20 (t, J = 7.7 Hz, 1 H), 4.46 (d, J = 13.3 Hz, 1 H), 6.86 (s, 1 H), 7.52-7.73 (m, 5 H), 7.76-7.92 (m, 3 H) MS m/z 579 (M + H)+ 765

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indol-5-yl)phenyl]-8- (trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62-0.77 (m, 2 H), 0.87-0.97 (m, 2 H), 1.24-1.34 (m, 2 H), 1.97-2.15 (m, 3 H), 2.67-2.86 (m, 1 H), 3.54-3.68 (m, 2 H), 3.74-4.12 (m, 6 H), 4.20 (t, J = 8.0 Hz, 1 H), 4.46 (d, J = 13.3 Hz, 1 H), 6.65 (br. s., 1 H), 7.30 (t, J = 2.7 Hz, 1 H), 7.43- 7.55 (m, 2 H), 7.64 (d, J = 8.2 Hz, 2 H), 7.83 (d, J = 8.1 Hz, 2 H), 7.92 (s, 1 H), 8.40 (br. s., 1 H) MS m/z 578 (M + H)+ 766

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4-(1H-indazol-5-yl)phenyl]-8- (trifluoroacetyl)-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.69 (m, 2 H), 0.78-0.88 (m, 2 H), 1.59 (d, J = 13.5 Hz, 3 H), 1.90-2.08 (m, 2 H), 2.71 (br. s., 1 H), 3.46-3.60 (m, 2 H), 3.67-4.05 (m, 6 H), 4.14 (t, J = 7.8 Hz, 1 H), 4.38 (d, J = 13.5 Hz, 1 H), 7.19 (s, 2 H), 7.46-7.67 (m, 4 H), 7.73 (d, J = 8.0 Hz, 2 H), 7.93 (s, 1 H) MS m/z 579 (M + H)+ 767

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-methylpropanoyl)-2-[4′-(1- methyl-1H-pyrazol-4-yl)biphenyl-4-yl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.70 (m, 4 H), 1.03 (br. s., 6 H), 1.23 (s, 1 H), 1.30-1.42 (m, 1 H), 1.45- 1.59 (m, 2 H), 1.62-1.85 (m, 2 H), 2.61 (m, J = 5.5 Hz, 1 H), 2.86-3.02 (m, 1 H), 3.09-3.26 (m, 2 H), 3.46-3.62 (m, 1 H), 3.65-3.81 (m, 2 H), 3.86 (br. s., 1 H), 3.88 (s, 3 H), 3.97 (d, J = 12.1 Hz, 1 H), 4.10-4.19 (m, 1 H), 4.23-4.37 (m, 1 H), 7.66-7.73 (m, 2 H), 7.77 (d, J = 9.9 Hz, 4 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.94 (s, 1 H), 8.22 (s, 1 H) MS m/z 593 (M + H)+ 768

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(N,N-dimethylglycyl)-2-[4′-(1- methyl-1H-pyrazol-4-yl)biphenyl-4-yl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.51-0.71 (m, 2 H), 0.82 (br. s., 2 H), 1.06-1.31 (m, 3 H), 1.40-1.68 (m, 2 H), 1.77-2.05 (m, 3 H), 2.46 (br. s., 6 H), 2.67 (br. s., 1 H), 3.24-3.55 (m, 4 H), 3.55-3.72 (m, 1 H), 3.72-3.87 (m, 3 H), 3.90 (br. s., 3 H), 4.02-4.20 (m, 1 H), 4.25-4.51 (m, 1 H), 7.19 (s, 1 H), 7.45- 7.65 (m, 5 H), 7.65-7.84 (m, 3 H) MS m/z 608 (M + H)+ 769

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.56-0.88 (m, 4 H), 1.09 (t, J = 6.8 Hz, 1 H), 1.18-1.30 (m, 1 H), 1.30-1.48 (m, 1 H), 1.63 (d, J = 12.5 Hz, 2 H), 1.91 (t, J = 10.2 Hz, 2 H), 2.55-2.74 (m, 1 H), 2.95 (s, 2 H), 3.08-3.28 (m, 3 H), 3.35- 3.44 (m, 3 H), 3.50-3.66 (m, 2 H), 3.67- 3.84 (m, 2 H), 3.83-3.86 (m, 2 H), 3.88 (s, 3 H), 4.15 (t, J = 8.2 Hz, 1 H), 7.66- 7.73 (m, 2 H), 7.77 (d, J = 7.6 Hz, 4 H), 7.83-7.99 (m, 3 H), 8.22 (s, 1 H) MS m/z 601 (M + H)+ 770

8-(Cyclopropylcarbonyl)-3-{[1- (cyclopropylcarbonyl)azetidin-3- yl]methyl}-2-[4′-(1-methyl-1H-pyrazol-4- yl)biphenyl-4-yl]-1,3,8-triazaspiro[4.5]dec- 1-en-4-one ¹H NMR (300 MHz, DMSO-d₆) δ ppm 0.53-0.67 (m, 4 H), 0.67-0.83 (m, 4 H), 1.23 (br. s., 1 H), 1.29-1.43 (m, 1 H), 1.43-1.63 (m, 2 H), 1.63-1.76 (m, 1 H), 1.76-1.92 (m, 1 H), 1.92-2.15 (m, 1 H), 2.54-2.69 (m, 1 H), 3.12-3.27 (m, 2 H), 3.52-3.79 (m, 3 H), 3.79-3.86 (m, 1 H), 3.88 (s, 3 H), 4.14 (t, J = 7.0 Hz, 1 H), 4.20- 4.37 (m, 2 H), 7.70 (m, J = 8.0 Hz, 2 H), 7.76 (d, J = 10.0 Hz, 4 H), 7.85-7.96 (m, 3 H), 8.22 (s, 1 H) MS m/z 591 (M + H)+ 771

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(1-methylethyl)-2-[4′-(1- methyl-1H-pyrazol-4-yl)biphenyl-4-yl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.56-0.68 (m, 2 H), 0.75-0.89 (m, 2 H), 1.01-1.28 (m, 6 H), 1.49-1.88 (m, 5 H), 2.03-2.29 (m, 2 H), 2.67 (dt, J = 13.4, 6.6 Hz, 1 H), 2.83-3.20 (m, 4 H), 3.47 (dd, J = 9.1, 5.8 Hz, 1 H), 3.71-3.88 (m, 3 H), 3.90 (s, 3 H), 4.11 (t, J = 7.9 Hz, 1 H), 7.19 (s, 1 H), 7.48-7.63 (m, 6 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.74 (s, 1 H) MS m/z 565 (M + H)+ 772

3-{[1-(Cyclopropylcarbonyl)azetidin-3- yl]methyl}-8-(2-hydroxyethyl)-2-[4′-(1- methyl-1H-pyrazol-4-yl)biphenyl-4-yl]- 1,3,8-triazaspiro[4.5]dec-1-en-4-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.54-0.68 (m, 2 H), 0.75-0.88 (m, 2 H), 1.56 (d, J = 13.3 Hz, 2 H), 1.76-2.15 (m, 6 H), 2.59-2.71 (m, 2 H), 2.78 (t, J = 10.6 Hz, 2 H), 2.86-3.02 (m, 2 H), 3.63 (t, J = 4.7 Hz, 2 H), 3.71-3.88 (m, 3 H), 3.90 (s, 3 H), 4.11 (t, J = 8.1 Hz, 1 H), 7.19 (s, 1 H), 7.47-7.63 (m, 6 H), 7.69 (d, J = 8.1 Hz, 2 H), 7.74 (s, 1 H) MS m/z 567 (M + H)+ 829

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(4-(2-(4-methylpiperazin-1- yl)pyridin-4-yl)phenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 541.3 (M + H)+ 828

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(4-(2-(piperazin-1-yl)pyridin- 4-yl)phenyl)-1,3-diazaspiro[4.4]non-1-en- 4-one MS m/z 527.2 (M + H)+ 822

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-methyl-4-(4-methyl-3,4- dihydro-2H-pyrido[3,2-b][1,4]oxazin-7- yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 528.3 (M + H)+ 845

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(1H-indol-5- yl)phenyl)-1,3-diazaspiro[4.4]non-1- en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) ppm 0.66-0.79 (m, 2 H), 0.89-1.01 (m, 2 H), 1.45-1.55 (m, 1.5 H), 1.58-1.68 (m, 1.5 H), 1.80-1.91 (m, 0.5 H), 1.94- 2.03 (m, 4 H), 2.06-2.17 (m, 4 H), 2.35- 2.46 (m, 0.5 H), 2.46-2.58 (m, 0.5 H), 3.01 (dd, J = 12.1, 7.1 Hz, 0.5 H), 3.16- 3.24 (m, 0.5 H), 3.31 (dt, J = 11.6, 8.1 Hz, 0.5 H), 3.49-3.58 (m, 2 H), 3.62-3.70 (m, 2 H), 6.66 (br. s., 1 H), 7.31 (d, J = 3.0 Hz, 1 H), 7.42-7.54 (m, 3 H), 7.60 (d, J = 5.1 Hz, 2 H), 7.91 (s, 1 H), 8.46 (br. s., 1 H). MS m/z 499.2 (M + H)+ 805

5-(2-methyl-4-(1-methyl-1H-indazol-5- yl)phenyl)-6-((1-nicotinoylazetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 505.2 (M + H)+ 796

6-((1-(1- hydroxycyclobutanecarbonyl)azetidin-3- yl)methyl)-5-(2-methyl-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498.3 (M + H)+ 851

(R)-5-(4-(1H-indol-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 467 (M + H)+ 823

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 820

(R)-5-(3″-chloro-[1,1′:4′,1″-terphenyl]-4- yl)-6-((1-(cyclopropanecarbonyl)piperidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 538 (M + H)+ 821

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4″-methyl-[1,1′:4′,1″- terphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 518 (M + H)+ 848

(R)-4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-[1,1′-biphenyl]-3-carboxylic acid MS m/z 458 (M + H)+ 819

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 818

(S)-5-(4-(benzofuran-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ms m/z 468 (M + H)+ 817

(S)-5-(4-(benzo[b]thiophen-5-yl)phenyl)- 6-((1-(cyclopropanecarbonyl)piperidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 484 (M + H)+ 843

(S)-5-(4-(1H-indol-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one m/z 467 (M + H)+ 816

(S)-5-(4-(1H-indazol-5-yl)phenyl)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 468 (M + H)+ 815

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 508 (M + H)+ 813

(S)-5-(3″-chloro-[1,1′:4′,1″-terphenyl]-4- yl)-6-((1-(cyclopropanecarbonyl)pipendin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 538 (M + H)+ 812

(S)-6-((1- (cyclopropanecarbonyl)pipendin-3- yl)methyl)-5-(4″-methyl-[1,1′:4′,1″- terphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 518 (M + H)+ 811

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2-isopropyl-2H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 496 (M + H)+ 809

(R)-7-(4-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-3,4-dihydroquinolin- 2(1H)-one MS m/z 483 (M + H)+ 802

(R)-5-(4-(5-chloropyridin-3-yl)phenyl)-6- ((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 449 (M + H)+ 849

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-methyl-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 498 (M + H)+ 850

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(3-fluoro-4-(2- methylbenzo[b]thiophen-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 502 (M + H)+ 814

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)-3-methylphenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 482 (M + H)+ 827

6-((1-(cyclopropanecarbonyl)piperidin-4- yl)methyl)-5-(4″-(1-methyl-1H-pyrazol-4- yl)-[1,1′:4′,1″-terphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 584 (M + H)+ 836

5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-methylphenyl)-1-methyl-1H- indazole-3-carbonitrile MS m/z 493 (M + H)+ 847

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 482 (M + H)+ 846

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2,3-dimethylbenzofuran- 5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 468 (M + H)+ 806

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-morpholinopyridin-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 486 (M + H)+ 807

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-isopropyl-1H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 808

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2-isopropyl-2H-indazol-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 482 (M + H)+ 803

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-cyclopropyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 480 (M + H)+ 804

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-(cyclopropylmethyl)- 1H-indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 494 (M + H)+ 801

5-(4-(1,5-naphthyridin-3-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 800

1-(5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)pyridin-2- yl)cyclopropanecarbonitrile MS m/z 466 (M + H)+ 797

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-(2-hydroxypropan-2- yl)pyridin-3-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 794

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(5-(2-hydroxypropan-2- yl)pyridin-2-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 459 (M + H)+ 798

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-cyclopropylpyridin-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 441 (M + H)+ 842

3-(5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2H-indazol-2- yl)propanenitrile MS m/z 493 (M + H)+ 792

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-methyl-1H- pyrazolo[4,3-b]pyridin-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 795

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-propylpyridin-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 443 (M + H)+ 838

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4′-(1-(oxetan-3-yl)-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 522 (M + H)+ 789

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(1-(oxetan-3-yl)- 1H-indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 514 (M + H)+ 788

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(1-(oxetan-3-yl)-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 777

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-fluoro-3′-(methylsulfonyl)- [1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 496 (M + H)+ 775

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3-methyl-3′- (methylsulfonyl)-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 492 (M + H)+ 776

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(3′-(isopropylsulfonyl)-3- methyl-[1,1′-biphenyl]-4-yl)-4,6- diazaspiro[2.4]hept-4-en-7-one MS m/z 520 (M + H)+ 841

5-(4-(7-bromoquinolin-2-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 529 (M + H)+ 839

5-(4-(7-bromo-3-methylquinolin-2- yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 840

7-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)quinolin-2(1H)-one MS m/z 467 (M + H)+ 793

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(3-methyl- [1,2,4]triazolo[4,3-a]pyridin-6-yl)phenyl)- 4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 455 (M + H)+ 791

5-(4-(7-bromo-4-methylquinolin-2- yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 543 (M + H)+ 790

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(2-methylquinolin-5- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 465 (M + H)+ 787

5-(4-(7-bromo-3-methylquinolin-2-yl)-2- methylphenyl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 571 (M + H)+ 786

5-(4′-(1-(cyclopropylmethyl)-1H-pyrazol- 5-yl)-3-methyl-[1,1′-biphenyl]-4-yl)-6-((1- (1-methylcyclopropanecarbonyl)azetidin- 3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en- 7-one MS m/z 548 (M + H)+ 785

5-(4′-(1-isobutyl-1H-pyrazol-5-yl)-3- methyl-[1,1′-biphenyl]-4-yl)-6-((1-(1- methylcyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 550 (M + H)+ 784

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(4-(6-isopropylpyridin-3- yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 443 (M + H)+ 844

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(5-(1-methyl-1H-indazol-5- yl)pyrazin-2-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one MS m/z 470 (M + H)+ 799

5-(4-(1,8-naphthyridin-3-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 452 (M + H)+ 837

5-(2-fluoro-4-(1-(2-hydroxyethyl)-1H- indazol-5-yl)phenyl)-6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 518 (M + H)+ 834

5-(4-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3-fluorophenyl)-1-methyl-1H- indazole-3-carbonitrile MS m/z 497 (M + H)+ 783

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N- methylcyclopropanecarboxamide MS m/z 515 (M + H)+ 778

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N- methylcyclopropanecarboxamide MS m/z 529 (M + H)+ 782

(R)-N-(4′-(6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)- N-methylcyclopropanecarboxamide MS m/z 525 (M + H)+ 779

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)- N-methylcyclopropanecarboxamide MS m/z 511 (M + H)+ 780

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-methyl-[1,1′-biphenyl]-3-yl)- N-methylcyclopropanesulfonamide MS m/z 547 (M + H)+ 781

N-(4′-(6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)-3′-fluoro-[1,1′-biphenyl]-3-yl)-N- methylcyclopropanesulfonamide MS m/z 551 (M + H)+ 855

(R)-2-(4-(5-chloropyridin-3-yl)-2- methylphenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 491.2 (M + H)+ 867

(R)-5-(4-(5-aminopyridin-3-yl)phenyl)-6- ((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 430 (M + H)+ 859

6-((1-(cyclopropanecarbonyl)piperidin-4- yl)methyl)-5-(4′-(trifluoromethyl)-[1,1′- biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4- en-7-one ms m/z 496 (M + H)+ 868

5-(4-(benzo[d]thiazol-2-yl)-2- fluorophenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.62 (dd, J = 7.4, 3.3 Hz, 2 H), 0.76- 0.89 (m, 2 H), 1.21 (td, J = 7.9, 4.1 Hz, 1 H), 1.69-1.79 (m, 2 H), 1.79-1.91 (m, 2 H), 2.66-2.85 (m, 1 H), 3.48 (dd, J = 9.7, 5.7 Hz, 1 H), 3.63-3.77 (m, 1 H), 3.78- 3.98 (m, 3 H), 4.17 (t, J = 8.3 Hz, 1 H), 7.39 (t, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.89 (d, J = 7.8 Hz, 1 H), 7.92-8.01 (m, 2 H), 8.05 (d, J = 8.1 Hz, 1 H). MS m/z 541.3 (M + H)+ 869

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(2-methyl-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.51-0.66 (m, 2 H), 0.77-0.87 (m, 2 H), 1.18-1.27 (m, 1 H), 1.66-1.76 (m, 2 H), 1.76-1.86 (m, 2 H), 2.42 (s, 3 H), 2.69-2.88 (m, 1 H), 3.47-3.58 (m, 1 H), 3.68-3.80 (m, 1 H), 3.80-3.91 (m, 2 H), 3.94 (s, 1 H), 4.16 (t, J = 8.3 Hz, 1 H), 6.23 (s, 1 H), 7.30 (s, 2 H), 7.37-7.56 (m, 3 H), 7.70 (s, 1 H), 7.97 (br. s., 1 H). MS m/z 541.3 (M + H)+ 870

6-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept- 4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.60 (br. s., 2 H), 0.81 (br. s., 2 H), 1.21 (br. s., 1 H), 1.72 (br. s., 2 H), 1.80 (br. s., 2 H), 2.67-2.90 (m, 1 H), 3.43- 3.59 (m, 1 H), 3.71 (br. s., 1 H), 3.77 (s, 3 H), 3.83 (d, J = 8.2 Hz, 3 H), 4.16 (br. s., 1 H), 6.49 (br. s., 1 H), 6.98-7.12 (m, 1 H), 7.28-7.61 (m, 5 H), 7.81 (br. s., 1 H). MS m/z 527.2 (M + H)+ 871

(R)-6-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-5-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-4,6- diazaspiro[2.4]hept-4-en-7-one ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.64-0.76 (m, 2 H), 0.85-0.99 (m, 2 H), 1.42-1.55 (m, 1.5 H), 1.59-1.73 (m, 0.5 H), 1.76-1.84 (m, 2 H), 1.86- 1.92 (m, 2 H), 1.94-2.06 (m, 1 H), 2.35- 2.51 (m, 1 H), 2.99 (dd, J = 12.0, 7.3 Hz, 0.5 H), 3.16-3.38 (m, 1 H), 3.44-3.68 (m, 3 H), 3.68-3.76 (m, 1.5 H), 4.13 (s, 3 H), 7.43-7.55 (m, 2 H), 7.55-7.70 (m, 3 H), 7.98 (s, 1 H), 8.07 (s, 1 H). MS m/z 509.9 (M + H)+ 872

6-(3-fluoro-4-(6-((1-(1- hydroxycyclopropanecarbonyl)azetidin-3- yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept- 4-en-5-yl)phenyl)-2-naphthonitrile ¹H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.85 (br. s., 2 H), 1.15 (d, J = 7.0 Hz, 2 H), 1.67-1.78 (m, 2 H), 1.78-1.89 (m, 2 H), 2.37 (br. s., 1 H), 2.77 (br. s., 1 H), 3.57 (br. s., 1 H), 3.71-3.88 (m, 2 H), 4.00 (br. s., 2 H), 4.35 (br. s., 1 H), 7.52 (d, J = 10.7 Hz, 1 H), 7.56-7.66 (m, 3 H), 7.76-7.84 (m, 1 H), 7.90-8.00 (m, 2 H), 8.06 (s, 1 H), 8.22 (s, 1 H). MS m/z 509 (M + H)+ 873

(R)-2-(4-(1H-indol-6-yl)-2-methylphenyl)- 3-((1-(cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.65-0.79 (m, 2 H), 0.87-1.02 (m, 2 H), 1.44-1.55 (m, 1.5 H), 1.60-1.68 (m, 1.5 H), 1.68 (br. s., 0.5 H), 1.93- 2.05 (m, 4 H), 2.06-2.20 (m, 4 H), 2.42 (s, 3 H), 2.44-2.52 (m, 0.5 H), 3.01 (dd, J = 11.9, 6.8 Hz, 0.5 H), 3.13-3.23 (m, 0.5 H), 3.27-3.44 (m, 1 H), 3.46-3.70 (m, 4 H), 6.60 (br. s., 1 H), 7.29 (d, J = 4.0 Hz, 1 H), 7.34-7.44 (m, 2 H), 7.53-7.64 (m, 3 H), 7.73 (dd, J = 8.3, 3.3 Hz, 1 H), 8.64 (s, 0.5 H), 8.62 (s, 0.5 H). MS m/z 595.3 (M + H)+ 874

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(1H-indol-6- yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.63-0.77 (m, 2 H), 0.83-0.96 (m, 2 H), 1.35-1.49 (m, 1.5 H), 1.56 (dd, J = 12.6, 7.6 Hz, 0.5 H), 1.78-1.89 (m, 0.5 H), 1.89-2.08 (m, 5 H), 2.14 (br. s., 4 H), 2.30-2.45 (m, 0.5 H), 2.45-2.59 (m, 0.5 H), 2.97 (dd, J = 12.4, 7.3 Hz, 0.5 H), 3.17 (t, J = 8.8 Hz, 0.5 H), 3.28 (d, J = 11.6 Hz, 0.5 H), 3.42-3.54 (m, 1.5 H), 3.60-3.74 (m, 2.5 H), 6.53 (br. s., 1 H), 7.25 (br. s., 1 H), 7.29 (d, J = 8.6 Hz, 1 H), 7.48 (s, 0.5 H), 7.45 (s, 0.5 H), 7.58 (br. s., 2 H), 7.63- 7.72 (m, 2 H), 8.41 (br. s., 1 H) MS m/z 499.2 (M + H)+ 875

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(quinolin-7- yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.65-0.78 (m, 2 H), 0.87-1.02 (m, 2 H), 1.44-1.56 (m, 1.5 H), 1.58-1.71 (m, 0.5 H), 1.80-1.91 (m, 1 H), 1.95- 2.13 (m, 8 H), 2.41 (dt, J = 14.4, 7.5 Hz, 0.5 H), 2.47-2.59 (m, 0.5 H), 3.00 (dd, J = 11.9, 7.3 Hz, 0.5 H), 3.19-3.27 (m, 0.5 H), 3.32 (dt, J = 12.0, 7.9 Hz, 0.5 H), 3.48- 3.59 (m, 2 H), 3.60-3.72 (m, 2.5 H), 7.49 (dd, J = 8.1, 4.0 Hz, 1 H), 7.57-7.65 (m, 1 H), 7.65-7.76 (m, 2 H), 7.81-7.87 (m, 1 H), 7.98 (d, J = 8.6 Hz, 1 H), 8.25 (d, J = 8.1 Hz, 1 H), 8.39 (s, 1 H), 8.94-9.10 (m, 1 H). MS m/z 511.2 (M + H)+ 876

(R)-2-(4-(benzo[b]thiophen-5-yl)-2- fluorophenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.64-0.77 (m, 2 H), 0.91 (br. s., 2 H), 1.39-1.48 (m, 1.5 H), 1.56 (dd, J = 12.9, 7.8 Hz, 0.5 H), 1.78-1.88 (m, 0.5 H), 1.90-2.06 (m, 4.5 H), 2.13 (br. s., 4 H), 2.31-2.41 (m, 0.5 H), 2.42-2.57 (m, 0.5 H), 2.97 (dd, J = 12.1, 7.6 Hz, 0.5 H), 3.13-3.21 (m, 0.5 H), 3.22-3.33 (m, 0.5 H), 3.44-3.54 (m, 1.5 H), 3.55-3.72 (m, 3 H), 7.35 (d, J = 5.1 Hz, 1 H), 7.45-7.54 (m, 3 H), 7.61 (d, J = 7.1 Hz, 1 H), 7.68- 7.77 (m, 1 H), 7.92 (d, J = 8.6 Hz, 1 H), 8.00 (s, 1 H). MS m/z 516.2 (M + H)+ 877

(R)-2-(4-(1H-benzo[d]imidazol-5-yl)-2- fluorophenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.60-0.72 (m, 2 H), 0.78-0.93 (m, 2 H), 1.31-1.49 (m, 1.5 H), 1.57 (dd, J = 12.6, 8.1 Hz, 0.5 H), 1.76 (dd, J = 10.9, 5.3 Hz, 0.5 H), 1.82-2.07 (m, 8.5 H), 2.23-2.38 (m, 0.5 H), 2.38-2.51 (m, 0.5 H), 2.89 (dd, J = 11.9, 7.3 Hz, 0.5 H), 3.10- 3.27 (m, 1 H), 3.37-3.49 (m, 2 H), 3.50- 3.63 (m, 2.5 H), 7.30-7.53 (m, 4 H), 7.58-7.70 (m, 2 H), 8.06 (s, 1 H). MS m/z 500.2 (M + H)+ 878

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1- (1-hydroxycyclopropanecarbonyl)pyrrolidin- 3-yl)methyl)-1,3-diazaspiro[4.4]non-1-en- 4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.90-1.01 (m, 2 H), 1.17 (br. s., 2 H), 1.51 (br. s., 0.5 H), 1.65 (br. s., 0.5 H), 1.90-2.11 (m, 5 H), 2.14-2.33 (m, 4 H), 2.49 (br. s., 1 H), 3.09 (br. s., 0.5 H), 3.44 (br. s., 0.5 H), 3.50 (s, 1.5 H), 3.72 (br. s., 0.5 H), 3.92 (d, J = 7.3 Hz, 3 H), 6.85 (d, J = 1.5 Hz, 1 H), 7.57 (d, J = 2.0 Hz, 1 H), 7.58-7.64 (m, 1 H), 7.70 (d, J = 2.2 Hz, 1 H), 7.79-7.89 (m, 5 H). MS m/z 498.2 (M + H)+ 879

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(1H-indazol-6- yl)phenyl)-1,3-diazaspiro[4.4]non-1-en-4- one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.69 (d, J = 7.6 Hz, 2 H), 0.82-0.96 (m, 2 H), 1.43 (dd, J = 7.8, 4.8 Hz, 1.5 H), 1.57 (br. s., 0.5 H), 1.81 (br. s., 0.5 H), 1.90-2.10 (m, 4.5 H), 2.14 (br. s., 4 H), 2.36 (br. s., 0.5 H), 2.52 (br. s., 0.5 H), 2.86-2.97 (m, 0.5 H), 3.18 (t, J = 8.6 Hz, 0.5 H), 3.23-3.34 (m, 0.5 H), 3.39-3.56 (m, 2 H), 3.58 (br. s., 1 H), 3.64 (br. s., 1.5 H), 7.28 (d, J = 8.1 Hz, 1 H), 7.36- 7.49 (m, 2 H), 7.61-7.75 (m, 2 H), 7.79 (d, J = 8.1 Hz, 1 H), 8.11 (s, 1 H). MS m/z 500.1 (M + H)+ 880

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(1-methyl-1H- indazol-5-yl)phenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.65-0.76 (m, 2 H), 0.84-0.97 (m, 2 H), 1.35-1.49 (m, 1.5 H), 1.50-1.63 (m, 0.5 H), 1.84 (br. s., 0.5 H), 1.91-2.05 (m, 5 H), 2.12 (br. s., 3.5 H), 2.31-2.41 (m, 0.5 H), 2.50 (d, J = 7.6 Hz, 0.5 H), 2.96 (dd, J = 12.1, 7.1 Hz, 0.5 H), 3.13-3.34 (m, 0.5 H), 3.43-3.54 (m, 2 H), 3.55- 3.70 (m, 3 H), 4.07 (s, 3 H), 7.43-7.51 (m, 2 H), 7.59 (t, J = 9.9 Hz, 2 H), 7.65- 7.74 (m, 1 H), 7.93 (s, 1 H), 8.04 (s, 1 H). MS m/z 514.2 (M + H)+ 881

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(2-fluoro-4-(1H-pyrrolo[2,3- b]pyridin-5-yl)phenyl)-1,3- diazaspiro[4.4]non-1-en-4-one ¹H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.55-0.69 (m, 2 H), 0.79-0.94 (m, 2 H), 1.31-1.48 (m, 1.5 H), 1.55 (dd, J = 12.6, 8.1 Hz, 0.5 H), 1.70-1.80 (m, 0.5 H), 1.81-2.06 (m, 8.5 H), 2.25-2.36 (m, 0.5 H), 2.37-2.49 (m, 0.5 H), 2.88 (dd, J = 11.9, 7.3 Hz, 0.5 H), 3.07-3.17 (m, 0.5 H), 3.22 (dt, J = 11.5, 8.1 Hz, 0.5 H), 3.36- 3.49 (m, 2 H), 3.50-3.64 (m, 2.5 H), 6.55 (d, J = 3.5 Hz, 1 H), 7.33-7.44 (m, 2 H), 7.46-7.59 (m, 2 H), 8.12 (s, 1 H), 8.49 (br. s., 1 H), 9.63 (s, 0.5 H), 9.59 (s, 0.5 H). MS m/z 500.3 (M + H)+ 882

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(3-methyl-4′-(5-methyl-1,3,4- oxadiazol-2-yl)-[1,1′-biphenyl]-4-yl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 538.2 (M + H)+ 883

(R)-2-(4-(benzo[d][1,3]dioxol-5-yl)-2- methylphenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 500.3 (M + H)+ 884

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(4-(2,3-dihydrobenzofuran-5- yl)-2-methylphenyl)-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 498.2 (M + H)+ 885

(R)-5-(4-(3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-4-oxo-1,3-diazaspiro[4.4]non- 1-en-2-yl)-3-fluorophenyl)-1H- benzo[d]imidazol-2(3H)-one MS m/z 516.2 (M + H)+ 886

(R)-2-(4′-acetyl-3-fluoro-[1,1′-biphenyl]-4- yl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-1,3-diazaspiro[4.4]non-1-en-4- one MS m/z 502.2 (M + H)+ 887

5-(4-(5-bromopyridin-2-yl)phenyl)-6-((1- (cyclopropanecarbonyl)azetidin-3- yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7- one MS m/z 479 (M + H)+ 888

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (methylsulfonyl)azetidin-3-yl)methyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 494.1 (M + H)+ 889

(S)-methyl 3-((2-(4-(benzofuran-5- yl)phenyl)-4-oxo-8-oxa-1,3- diazaspiro[4.5]dec-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 488.1 (M + H)+ 890

(R)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-3-((1-(2,2,2- trifluoroacetyl)pyrrolidin-3-yl)methyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 540.2 (M + H)+ 891

(S)-methyl 6-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-7-((1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-8- oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 577.3 (M + H)+ 892

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- (((R)-1-(thiazole-2-carbonyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 541.1 (M + H)+ 893

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2- trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 552.3 (M + H)+ 894

(3S)-methyl 3-((2-(4′-(1-methyl-1H- pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4-oxo-7- oxa-1,3-diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 514.2 (M + H)+ 895

2-(4-(quinolin-7-yl)phenyl)-3-((1-(2,2,2- trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 509.1 (M + H)+ 896

3-((1-(methylsulfonyl)pyrrolidin-3- yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 505.2 (M + H)+ 897

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)- 7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 498.2 (M + H)+ 898

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (methylsulfonyl)azetidin-3-yl)methyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 480.2 (M + H)+ 899

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2- trifluoroacetyl)azetidin-3-yl)methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 538.2 (M + H)+ 900

(S)-methyl 7-((1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-8- oxo-6-(4-(quinolin-7-yl)phenyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 548.2 (M + H)+ 901

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(thiazole-2- carbonyl)azetidin-3-yl)methyl)-7-oxa-1,3- diazaspiro[4.4]non-1-en-4-one MS m/z 553.2 (M + H)+ 902

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(methylsulfonyl)azetidin-3-yl)methyl)- 8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 508.1 (M + H)+ 903

methyl 3-((4-oxo-2-(4-(quinolin-7- yl)phenyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 471.2 (M + H)+ 904

methyl 3-((2-(4-(benzofuran-5-yl)phenyl)- 4-oxo-7-oxa-1,3-diazaspiro[4.4]non-1-en- 3-yl)methyl)azetidine-1-carboxylate MS m/z 460.2 (M + H)+ 905

methyl 3-((2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4-oxo-7-oxa-1,3- diazaspiro[4.4]non-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z 474.3 (M + H)+ 906

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)- 6-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-8-oxo-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 557.2 (M + H)+ 907

(R)-methyl 6-(4-(1-methyl-1H-indazol-5- yl)phenyl)-8-oxo-7-((1-(2,2,2- trifluoroacetyl)pyrrolidin-3-yl)methyl)- 2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 569.1 (M + H)+ 908

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(thiazole-2-carbonyl)azetidin-3- yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 541.1 (M + H)+ 909

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(thiazole-2-carbonyl)azetidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 527.1 (M + H)+ 910

2-(4-(quinolin-7-yl)phenyl)-3-((1-(2,2,2- trifluoroacetyl)azetidin-3-yl)methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 523.2 (M + H)+ 911

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(thiazole-2- carbonyl)azetidin-3-yl)methyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one MS m/z 567.2 (M + H)+ 912

3-((1-(methylsulfonyl)azetidin-3- yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 505.2 (M + H)+ 913

(S)-2-(4-(benzofuran-5-yl)phenyl)-3-((1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 508.1 (M + H)+ 914

2-(4-(benzofuran-5-yl)phenyl)-3-(((S)-1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 494.1 (M + H)+ 915

(3S)-methyl 3-((2-(4-(1-methyl-1H- indazol-5-yl)phenyl)-4-oxo-7-oxa-1,3- diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 488.2 (M + H)+ 916

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)- 6-(4-(1-methyl-1H-indazol-5-yl)phenyl)-8- oxo-2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 531.2 (M + H)+ 917

(S)-methyl 6-(4-(1-methyl-1H-indazol-5- yl)phenyl)-7-((1-(methylsulfonyl)pyrrolidin- 3-yl)methyl)-8-oxo-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 551.3 (M + H)+ 918

(S)-2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 548.3 (M + H)+ 919

(R)-methyl 6-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1-(2,2,2- trifluoroacetyl)pyrrolidin-3-yl)methyl)- 2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 595.1 (M + H)+ 920

2-(4-(quinolin-7-yl)phenyl)-3-(((R)-1- (thiazole-2-carbonyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 538.1 (M + H)+ 921

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1- (methylsulfonyl)azetidin-3-yl)methyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 534.2 (M + H)+ 922

methyl 3-((4-oxo-2-(4-(quinolin-7- yl)phenyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-3-yl)methyl)azetidine-1-carboxylate MS m/z 485.2 (M + H)+ 923

(R)-methyl 6-(4-(1-methyl-1H-indazol-5- yl)phenyl)-8-oxo-7-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 584.2 (M + H)+ 924

(S)-methyl 6-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1- (pyrrolidine-1-carbonyl)pyrrolidin-3- yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 596.3 (M + H)+ 925

(R)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)+ 926

(S)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-3-((1-(methylsulfonyl)pyrrolidin- 3-yl)methyl)-8-oxa-1,3- diazaspiro[4.5]dec-1-en-4-one MS m/z 522.1 (M + H)+ 927

methyl 3-((2-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4-oxo-7-oxa-1,3- diazaspiro[4.4]non-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z 500.2 (M + H)+ 928

methyl 3-((2-(4-(benzofuran-5-yl)phenyl)- 4-oxo-8-oxa-1,3-diazaspiro[4.5]dec-1-en- 3-yl)methyl)azetidine-1-carboxylate MS m/z 474.2 (M + H)+ 929

(R)-methyl 6-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-8-oxo-7-((1- (thiazole-2-carbonyl)pyrrolidin-3- yl)methyl)-2,5,7-triazaspiro[3.4]oct-5-ene- 2-carboxylate MS m/z 610.1 (M + H)+ 930

2-(4-(quinolin-7-yl)phenyl)-3-((1-(thiazole- 2-carbonyl)azetidin-3-yl)methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 524.1 (M + H)+ 931

(S)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 7-((1-(methoxycarbonyl)pyrrolidin-3- yl)methyl)-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z 517.1 (M + H)+ 932

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (thiazole-2-carbonyl)azetidin-3-yl)methyl)- 7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 513.1 (M + H)+ 933

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- (((S)-1-(methylsulfonyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 508.1 (M + H)+ 934

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (thiazole-2-carbonyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 527.1 (M + H)+ 935

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(2,2,2-trifluoroacetyl)azetidin-3- yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 526.2 (M + H)+ 936

methyl 3-((2-(4′-(1-methyl-1H-pyrazol-4- yl)-[1,1′-biphenyl]-4-yl)-4-oxo-8-oxa-1,3- diazaspiro[4.5]dec-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z 514.2 (M + H)+ 937

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(2,2,2-trifluoroacetyl)azetidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 512.3 (M + H)+ 938

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (2,2,2-trifluoroacetyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one m/z 512.2 (M + H)+ 939

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1- (methylsulfonyl)pyrrolidin-3-yl)methyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 534.2 (M + H)+ 940

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(2,2,2- trifluoroacetyl)pyrrolidin-3-yl)methyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 552.2 (M + H)+ 941

methyl 3-((2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-4-oxo-8-oxa-1,3- diazaspiro[4.5]dec-1-en-3- yl)methyl)azetidine-1-carboxylate MS m/z 488.2 (M + H)+ 942

3-((1-(methylsulfonyl)azetidin-3- yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 491.2 (M + H)+ 943

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-7-oxa- 1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 567.2 (M + H)+ 944

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(methylsulfonyl)azetidin-3-yl)methyl)- 7-oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 494.2 (M + H)+ 945

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- ((1-(pyrrolidine-1-carbonyl)azetidin-3- yl)methyl)-7-oxa-1 ,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 513.3 (M + H)+ 946

(R)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 8-oxo-7-((1-(2,2,2- trifluoroacetyl)pyrrolidin-3-yl)methyl)- 2,5,7-triazaspiro[3.4]oct-5-ene-2- carboxylate MS m/z 555.1 (M + H)+ 947

2-(4-(quinolin-7-yl)phenyl)-3-((1-(thiazole- 2-carbonyl)azetidin-3-yl)methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 538.1 (M + H)+ 948

(R)-2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 581.2 (M + H)+ 949

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (thiazole-2-carbonyl)azetidin-3-yl)methyl)- 8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 527.2 (M + H)+ 950

2-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′- biphenyl]-4-yl)-3-((1- (methylsulfonyl)azetidin-3-yl)methyl)-7- oxa-1,3-diazaspiro[4.4]non-1-en-4-one MS m/z 520.2 (M + H)+ 951

3-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-8-isopropyl-2-(4-(isoquinolin-6- yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en- 4-one MS m/z 536 (M + H)+ 952

3-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-8-(2,2,2-trifluoroacetyl)-2-(4-(1- (2,2,2-trifluoroacetyl)-1H-indol-5- yl)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en- 4-one MS m/z 578 (M + H)+ 953

(S)-methyl 3-((2-(4-(1-methyl-1H-indazol- 5-yl)phenyl)-4-oxo-8-oxa-1,3- diazaspiro[4.5]dec-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 502.2 (M + H)+ 954

(3S)-methyl 3-((2-(4-(benzofuran-5- yl)phenyl)-4-oxo-7-oxa-1,3- diazaspiro[4.4]non-1-en-3- yl)methyl)pyrrolidine-1-carboxylate MS m/z 474.2 (M + H)+ 955

2-(4-(1-methyl-1H-indazol-5-yl)phenyl)-3- (((R)-1-(2,2,2-trifluoroacetyl)pyrrolidin-3- yl)methyl)-7-oxa-1,3-diazaspiro[4.4]non- 1-en-4-one MS m/z 526.1 (M + H)+ 956

(S)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 7-((1-(methylsulfonyl)pyrrolidin-3- yl)methyl)-8-oxo-2,5,7-triazaspiro[3.4]oct- 5-ene-2-carboxylate MS m/z 537.1 (M + H)+ 957

(R)-methyl 6-(4-(benzofuran-5-yl)phenyl)- 8-oxo-7-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 570.2 (M + H)+ 958

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1- (thiazole-2-carbonyl)pyrrolidin-3- yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 541.1 (M + H)+ 959

(R)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-3-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-8-oxa- 1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 555.1 (M + H)+ 960

(S)-3-((1-(methylsulfonyl)pyrrolidin-3- yl)methyl)-2-(4-(quinolin-7-yl)phenyl)-8- oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 519.2 (M + H)+ 961

2-(4-(benzofuran-5-yl)phenyl)-3-((1- (2,2,2-trifluoroacetyl)azetidin-3-yl)methyl)- 8-oxa-1,3-diazaspiro[4.5]dec-1-en-4-one MS m/z 512.2 (M + H)+ 962

(R)-methyl 8-oxo-6-(4-(quinolin-7- yl)phenyl)-7-((1-(thiazole-2- carbonyl)pyrrolidin-3-yl)methyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 581.1 (M + H)+ 963

(S)-methyl 7-((1- (methoxycarbonyl)pyrrolidin-3-yl)methyl)- 8-oxo-6-(4-(quinolin-7-yl)phenyl)-2,5,7- triazaspiro[3.4]oct-5-ene-2-carboxylate MS m/z 528.3 (M + H)+ 964

3-((1-(cyclopropanecarbonyl)azetidin-3- yl)methyl)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-8-(2,2,2-trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 593 (M + H)+ 965

(R)-2-(4-(quinolin-7-yl)phenyl)-3-((1- (2,2,2-trifluoroacetyl)pyrrolidin-3- yl)methyl)-8-oxa-1,3-diazaspiro[4.5]dec- 1-en-4-one MS m/z 537.2 (M + H)+ 966

(R)-2-(4-(1H-indazol-5-yl)phenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-8-(2-hydroxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 541 (M + H)+ 967

(R)-2-(4-(1H-indol-5-yl)phenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-8-(2-hydroxyethyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 540 (M + H)+ 968

(R)-2-(4-(benzofuran-5-yl)phenyl)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-8-(2,2,2-trifluoroacetyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 593 (M + H)+ 969

(S)-6-((1- (cyclopropanecarbonyl)piperidin-3- yl)methyl)-5-(4′-hydroxy-[1,1′-biphenyl]-4- yl)-4,6-diazaspiro[2.4]hept-4-en-7-one MS m/z 444 (M + H)+ 970

(R)-3-((1- (cyclopropanecarbonyl)pyrrolidin-3- yl)methyl)-2-(4-(1-methyl-1H-indazol-5- yl)phenyl)-8-(methylsulfonyl)-1,3,8- triazaspiro[4.5]dec-1-en-4-one MS m/z 589 (M + H)+

BIOLOGICAL EXAMPLES Biological Example 1 Fatty Acid Synthase (FASN) Inhibition Scintillation Proximity Assay

In this assay, inhibition of FASN activity is measured using ³H-acetyl-CoA and malonyl-CoA as substrates. ³H-Acetyl CoA is converted to ³H-palmitate through a series of reactions by the FASN protein, which contains 7 functional domains and carries out 7 enzymatic reactions to ultimately produce ³H-palmitate. The assay principle is based upon the fact that ³H-acetyl-CoA is hydrophilic and the end product, ³H-palmitate is hydrophobic. The hydrophobic ³H-palmitate binds to scintillation proximity assay (SPA) imaging beads (resulting in light emission from the imaging beads) whereas the hydrophilic ³H-acetyl-CoA does not bind to the imaging beads (and therefore does not result in light emission from the imaging beads).

10 μL assay buffer (100 mM KH₂PO₄ pH 7.5, 1 mM DTT) (20 μL in blanks) was added to a 384-well white optiplate plate (Perkin Elmer). 0.9 μL test compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO and 10 μL hFASN enzyme (full length, 300 ng, purified in house) or 10 μL assay buffer was added to the wells. Then 10 μL 450 μM NADPH (Sigma N7505), 18.75 μM [³H]-acetyl-CoA (Perkin Elmer NET-290L),150 μM malonyl-CoA (Sigma M4263) were added, mixed and incubated at room temperature for 60 minutes. The reaction was stopped by adding 20 μL Streptavidin coupled imaging beads (25 mg/ml). After incubation for 30 minutes at room temperature in the dark, the 384 well plate was centrifuged at 1500 rpm for 3 minutes and was measured after at least 24 hrs by the LEADseeker™, measuring emission using a 610±20 nm pass filter. (Bays, N. W., et al., “A simplified scintillation proximity assay for fatty acid synthase activity: development and comparison with other FAS activity assays”, J. Biomol. Screen., 2009, pp 636-642, Vol. 14(6).)

Raw data generated by the instrument were normalized to % Controlmin values, which were calculated as:

% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and high control wells on the plate, after manual exclusion of outliers. A plot of Controlmin versus test compound concentration was fitted to a 4-parameter logistic curve using a non-linear least squares regression method. From the plot, an IC₅₀ (concentration at such 50% inhibition is achieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀), when IC₅₀ is expressed in molar units.

Representative compounds of formula (I) the present invention were tested according to the procedure as described in Biological Example 1 above, with results as listed in Table 6, below. Wherein the results listed below, the plC₅₀ value is preceded with a “˜”, the “˜” indicates that the standard error of the plC₅₀ value, as estimated by the non-linear regression algorithm, is larger than 0.5. This corresponds to a factor of uncertainly on the IC₅₀ that is larger than square root of 10 (>3.162).

TABLE 6 FASN pIC₅₀ Human FASN Human FASN ID No. pIC₅₀ % inhibition @ 10 μM 1 6.24 93 2 7.34 108.6 3 <5 44.3 4 7.47 102.6 5 5.67 74.6 6 5.14 61.6 7 <5 33.7 8 <5 5.1 9 <5 11.4 10 6.69 89.7 11 6.03 82.2 12 7.59 99.4 13 <5 29.7 14 6.83 98.2 15 7.36 113 16 5.86 72.5 17 6.64 97 18 <5 42.7 19 5.86 78 20 6.8 101 22 5.97 85 24 5.73 76.4 25 ~5.31 64.4 27 7.15 100.1 28 7.53 109.6 29 6.03 81.7 30 7.24 107.5 31 7.66 106.7 32 <5 6.8 33 7.59 109.4 34 6.93 101.7 35 7.08 106.8 36 6.26 96.2 37 <5 28.6 38 6.57 94.9 39 7.19 103 40 7.73 105.6 41 6.34 92.6 42 <5 23.5 43 ~5 45.4 44 <5 ~0.97 47 7.69 102.6 48 7.01 107.6 49 7.22 101.4 50 5.46 64.8 51 7.1 101.9 52 6.12 89.9 53 5.71 78.6 54 5.33 64.7 55 <5 32.7 56 6.39 89.2 57 6.12 88.1 58 7.6 107.7 59 7.38 98.7 60 7.03 99.4 61 5.4 63.2 62 <5 29.3 63 7.13 115 64 6.15 92.9 65 7.55 101.1 66 7.13 106.5 67 6.55 100.1 68 7.2 107 69 6.65 100.1 70 6.27 92.5 71 7.38 102 72 7.32 106.3 73 7.48 111.1 74 7.65 113.7 75 6.29 92.7 76 6.89 99.2 77 6.76 102.6 78 7.23 111.3 79 7.21 107.5 80 6.36 92.1 81 7.04 109.4 82 6.67 105.2 83 5.32 65.6 84 6.0 89.2 85 6.45 97.9 90 6.51 101 91 <5 21.3 92 7.29 111.3 93 7.12 115.8 94 6.84 110.8 95 <5 24.4 96 5.3 71.2 97 5.25 58.7 98 <5 35.1 99 5.33 61.4 100 7.13 110.2 101 7.09 112.1 102 6.68 106.6 103 7.17 108.6 104 5.49 71.7 105 7.0 104.1 106 6.95 109.9 107 <5 10.6 108 5.82 83.8 109 5.29 62.1 110 <5 32.6 111 5.36 62.2 112 7.3 104.2 113 6.93 109.4 114 7.12 106.9 115 7.52 113 116 7.55 121.2 117 6.69 107.7 118 6.45 101.1 119 6.76 107.4 120 7.41 115.9 121 7.04 115.1 122 6.91 112.3 123 5.9 81.5 124 6.94 113.2 125 5.4 64.6 126 6.19 96.3 127 6.31 106.7 129 5.93 90.7 130 5.42 74 131 5.05 52.1 132 5.77 83.7 133 6.35 99.1 134 6.25 91.7 135 5.61 78.9 136 5.53 77.7 137 6.75 111.6 138 6.41 101.5 139 6.76 111.5 140 6.65 113.9 141 6.6 110.3 142 7.16 119.3 143 7.44 118.6 144 7.2 116.6 145 6.4 105.5 146 <5 38 147 7.15 89.5 148 6.52 104.6 150 6.98 112.9 151 6.89 111.8 152 6.91 123 153 6.98 115.6 154 6.57 109.4 155 6.11 96.5 156 6.72 107.8 157 7.17 112.2 158 <5 33 159 7.1 116 160 <5 29.3 161 <5 16 162 5.96 90.9 163 6.64 110.5 164 7.4 115.2 165 6.64 108.3 166 5.47 71.6 167 6.28 96.4 168 6.84 108 169 <5 45.7 170 5.1 55.6 171 6.67 106.6 172 6.6 107.9 173 6.42 97 174 6.61 109.4 178 6.99 108 179 5.2 59.5 180 6.86 100.8 181 6.91 109.4 182 6.86 103.9 183 6.86 108.8 184 6.36 106.6 186 5.81 80.4 187 6.22 96.5 188 ~5 50.4 189 <5 16.7 190 6.53 105.2 191 7.1 108.3 192 6.23 94.3 200 7.46 102 201 7.36 100 202 7.08 101 203 7.24 99 204 7.24 103 205 7.01 94 206 7.43 101 207 7.08 101 208 7.19 99 209 7.05 108 210 7.05 103 211 7.07 107 212 7.55 101 213 7.33 95 214 7.65 99 215 7.63 102 216 7.54 102 217 7.54 103 218 7.14 95 219 7.12 103 220 7.04 99 221 7.01 92 222 7.56 103 223 7.27 104 224 7.6 103 225 7.42 95 226 7.63 98 227 7.37 99 228 7.35 103 230 7.39 107 231 7 108 232 7.08 105 233 7.3 110 234 7.68 108 235 7.63 111 236 7.46 98 237 7.1 100 238 7.36 98 239 7.23 96 240 7.91 101 241 7.66 100 242 7.72 103 243 7.65 104 244 7.25 101 245 7.49 98 246 7.77 101 247 7.79 103 248 7.16 99 249 7.77 102 250 7.31 100 251 7.49 101 252 7.57 100 253 7.45 97 254 7.53 100 255 7.2 99 256 7.27 95 257 7.31 99 258 7.14 94 259 7.6 95 260 7.79 101 261 7.26 98 262 ~7.29 94 263 7.29 105 264 7.43 108 265 7.34 103 266 7.47 102 267 7.58 97 268 7.26 104 269 7.65 102 270 7.45 102 271 7.25 104 272 7.73 105 273 7.37 102 274 7.3 101 278 7.59 113 279 7.55 107 280 7.52 109 281 7.35 114 282 7.06 106 283 7.38 112 284 7.59 106 286 7.36 103 287 7.36 110 288 7.57 107 289 7.01 102 290 7.1 110 291 7.56 108 292 7.06 100 293 7.42 105 294 7.37 100 295 7.27 100 296 7.41 106 297 7.5 111 298 7.66 100 299 7.64 101 300 7.24 102 301 7.7 99 302 7.48 101 303 7.51 102 304 7.01 99 305 7.6 103 306 7.3 98 307 7.17 100 308 7.32 102 309 7.7 101 310 7.4 102 311 7.6 101 312 7.12 101 313 7.41 99 314 7.39 103 315 7.18 98 316 7.38 108 317 7.24 103 318 7.18 100 319 7.54 105 320 7.59 102 321 7.52 99 322 7.42 102 323 7.6 101 324 7.49 105 325 7.1 100 326 7.4 103 327 7.49 104 328 7.5 98 331 7.18 100 332 7.73 100 333 7.26 98 334 7.66 97 335 7.19 105 336 7.3 103 337 7.44 105 338 7.36 106 339 7.51 95 340 7.54 101 341 7.19 102 342 7.16 106 343 7.29 98 344 7.59 99 345 7.05 99 346 7.31 97 347 7.31 98 348 7.2 96 349 7.78 102 350 7.82 99 351 7.13 95 352 7.13 94 353 7.26 101 354 7.3 100 355 7.52 96 356 6.99 99 357 7.4 97 358 7.51 100 359 7.4 95 361 7.4 103 362 7.11 96 363 7.4 94 364 7.24 89 365 7.63 97 366 7.21 89 368 7.55 90 369 7.58 102 370 7.54 100 371 7.25 101 372 7.79 101 374 7.59 99 375 7.36 103 377 7.45 100 378 7.41 100 379 7.7 102 380 7.18 100 381 7.64 98 382 7.6 99 383 7.62 102 384 7.2 100 385 7.64 103 387 6.66 103 388 6.45 99 389 5.14 56 390 6.49 99 391 6.89 104 392 6.61 91 393 ~5.54 62 394 5.97 84 395 5.2 54 396 ~5.07 52 397 6.1 90 398 6.58 102 399 6.44 99 400 6.71 101 401 5.43 70 402 6.86 102 404 6.75 97 405 6.89 102 406 6.9 99 407 5.63 69 408 5.29 63 409 6.76 100 410 6.6 96 411 6.8 100 412 6.49 96 413 6.52 91 414 6.87 101 415 5.9 80 416 ~5.75 76 417 5.28 62 418 6.82 103 419 6.29 96 420 6.31 92 421 6.34 94 422 5.48 70 423 6.5 90 424 5.4 68 425 6.56 93 426 6.46 94 427 6.38 91 428 6.86 101 429 6.62 96 430 5.05 52 431 6.5 97 432 6.85 98 433 5.74 72 434 5.69 73 435 6.58 91 436 ~5 43 437 5.56 72 438 5.48 65 439 5.02 48 440 6.71 97 441 5.4 63 442 6.7 94 443 6.04 88 444 6.6 95 445 6.74 100 446 5.3 60 447 5.92 79 448 5.07 50 449 6.26 89 450 6.53 98 451 5.9 82 452 6.64 97 453 6.61 94 454 ~5.22 53 455 6.79 99 456 5.16 65 457 6.34 91 458 5.09 48 459 5.06 43 460 5.51 63 461 6.85 95 462 6.8 98 463 6.65 93 464 5.39 66 465 6.82 99 466 6.32 87 467 6.48 93 468 6.37 90 469 6.93 97 470 6.74 98 471 6.74 99 472 6.89 97 473 6.57 95 474 6.91 99 475 6.78 93 476 6.58 90 477 5.51 67 478 5.86 92 479 6.79 95 480 6.81 97 481 5.66 68 482 5.88 76 483 6.97 95 484 6.82 99 485 6.79 96 486 5.82 81 487 5.93 81 488 6.67 88 489 6.93 97 490 6.48 81 491 6.94 100 492 6.0 77 493 6.78 98 494 6.66 95 495 6.59 95 496 6.52 94 497 6.23 87 498 6.94 99 499 6.61 96 500 ~5.56 74 501 5.08 52 502 6.45 94 503 5.24 58 504 5.07 42 505 5.93 80 506 5.47 61 507 6.38 89 508 5.54 74 509 5.7 69 510 6.02 80 511 6.45 94 512 6.17 87 513 5.91 85 514 5.13 56 515 6.74 96 516 5.93 83 517 6.19 88 518 ~5.33 62 519 6.8 96 520 6.37 97 521 6.29 94 522 5.78 79 523 6.29 92 524 5.68 73 525 5.98 84 526 6.04 93 527 5.8 83 528 6.44 105 529 6.99 96 530 6.58 97 531 6.77 96 532 5.27 58 533 5.12 54 534 6.79 95 535 5.0 53 536 5.91 88 537 6.76 99 538 6.77 99 539 ~5.2 54 540 5.3 64 541 6.96 100 542 6.16 89 543 6.84 97 544 6.69 98 545 6.96 101 546 6.69 100 547 6.75 98 548 6.79 88 549 5.75 83 550 5.74 80 551 ~5.12 57 552 5.31 66 553 5.87 85 554 6.89 97 555 5.73 75 556 5.28 61 557 6.43 97 558 6.73 96 559 5.22 59 560 5.43 68 561 ~5.14 56 562 6.61 97 563 6.2 88 564 6.58 97 566 6.42 93 568 6.89 89 569 6.68 86 570 5.38 65 571 5.86 79 572 6.87 87 573 6.78 88 574 6.09 82 575 5.09 52 576 6.42 99 577 5.63 67 578 6.19 92 579 5.96 83 580 6.91 108 581 6.5 93 582 6.49 103 583 5.4 74 584 6.87 91 585 6.95 99 586 6.28 93 587 5.48 70 588 6.22 93 589 5.02 52 590 5.76 80 591 6.71 93 592 5.53 70 593 5.15 56 594 6.61 102 595 5.87 83 596 6.73 102 597 ~5.37 65 598 6.68 103 599 6.95 102 600 6.38 98 601 6.73 100 602 6.49 94 603 5.94 87 604 5.95 84 605 5.18 62 606 6.68 97 607 6.8 102 608 6.83 98 609 6.73 99 610 5.98 87 611 ~5 46 612 5.69 74 613 6.94 102 614 6.82 102 615 6.49 98 616 6.29 94 617 6.78 100 618 6.64 98 619 6.73 101 620 5.4 71 621 6.21 92 622 5.8 82 623 6.84 101 624 5.65 76 627 6.97 105 628 6.93 100 629 5.13 55 630 5.5 67 631 5.07 47 632 5.56 70 633 5.08 56 634 5.52 68 635 6.66 97 636 5.17 59 637 6.92 99 638 6.72 100 639 6.55 97 640 5.27 64 641 6.94 102 642 6.66 99 643 6.42 96 644 6.75 97 645 6.56 100 646 5.93 88 647 6.2 91 648 5.59 74 649 6.8 97 650 5.87 84 651 5.51 77 652 6.73 97 653 5.52 71 654 5.94 83 655 6.75 99 656 5.7 74 657 6.51 97 658 5.06 52 659 ~5.08 38 660 5.65 76 661 7.23 95 662 6.52 98 663 7.19 100 664 5.43 87 665 6.49 94 666 ~5.3 62 667 6.81 97 668 5.93 86 669 6.77 96 670 ~5.12 56 671 5.78 76 672 6.34 92 673 5.26 61 674 6.34 94 675 5.55 66 676 6.57 98 677 ~5.15 63 678 6.43 95 679 ~5.21 57 680 7.1 98 681 6.53 91 682 6.94 96 683 5.38 63 684 5.37 61 685 6.07 84 686 6.74 98 687 5.54 73 688 6.67 99 689 5.39 61 690 6.26 86 691 ~5.13 63 692 6.1 99 693 5.01 48 694 5.61 69 695 5.23 43 696 5.77 72 697 5.23 58 698 6.6 92 699 ~6.14 89 700 6.62 94 701 6.32 95 702 ~5.58 75 703 5.35 61 704 6.06 86 705 5.57 71 706 ~5.63 65 707 5.19 55 708 5.73 76 709 5.39 64 710 5.55 66 711 5.22 60 712 5.61 69 713 ~5.17 59 714 6.44 89 715 6.14 86 716 6.4 88 717 6.17 87 718 ~5.62 72 719 5.41 67 720 6.11 87 721 5.24 63 722 5.18 56 723 5.1 55 724 5.38 47 725 6.61 93 726 5.71 73 727 6.69 98 728 7.19 100 729 6.51 95 730 7.0 102 731 5.42 63 732 ~5.92 88 733 6.7 96 734 5.77 84 735 6.87 97 736 5.38 51 737 6.52 97 738 5.72 80 739 6.63 92 740 5.05 46 741 6.8 102 742 6.72 99 743 6.15 90 744 6.94 98 745 7.15 104 746 6.56 94 747 7.07 96 748 6.45 99 749 6.86 97 750 6.51 94 751 6.87 98 752 6.11 91 753 6.87 107 754 5.53 67 755 6.64 107 756 5.8 82 757 6.8 104 758 5.47 71 759 5.04 38 760 5.32 62 761 ~5.12 45 762 6.5 95 763 ~5.27 63 764 ~5.36 63 765 6.44 96 766 ~5.35 67 767 5.72 76 768 5.84 79 769 5.3 60 770 5.66 77 771 5.12 44 772 5.4 64 775 <5 34 776 <5 25 777 <5 34 784 <5 14 785 <5 24 786 <5 31 787 <5 38 788 <5 14 789 <5 26 790 <5 47 791 <5 ~2 792 <5 38 793 <5 13 794 <5 ~15 795 <5 34 796 <5 19 797 <5 1 798 <5 30 799 <5 39 800 <5 16 801 <5 6 802 <5 24 803 <5 48 804 <5 41 805 <5 14 806 <5 ~6 807 <5 7 808 <5 31 809 <5 29 811 <5 35 812 <5 5 813 <5 2 814 <5 39 815 <5 1 816 <5 4 817 <5 1 818 <5 2 819 <5 10 820 <5 33 821 <5 7 822 <5 25 823 <5 31 828 <5 4 829 <5 7 845 7.7 106 855 <5 52 859 <5 11 867 <5 44 868 7.32 869 7.33 870 7.57 871 7.65 872 7.63 99 873 7.61 109 874 7.6 108 875 7.6 104 876 7.51 105 877 7.47 103 878 7.44 113 879 7.38 104 880 7.1 101 881 6.97 101 882 6.87 107 883 6.57 100 884 6.54 100 885 6.51 98 886 5.72 79 887 5.39 73 888 <5 1 889 <5 44 890 <5 37 891 <5 8 892 <5 ~29 893 <5 ~12 894 <5 20 895 <5 6 896 <5 10 897 <5 15 898 <5 6 899 <5 ~10 900 <5 9 901 <5 2 902 <5 6 903 <5 15 904 <5 ~24 905 <5 ~7 906 <5 14 907 <5 21 908 <5 2 909 <5 6 910 <5 12 911 <5 7 912 <5 1 913 <5 0.4 914 <5 1 915 <5 11 916 <5 20 917 <5 2 918 <5 2 919 <5 12 920 <5 35 921 <5 ~7 922 <5 38 923 <5 27 924 <5 41 925 <5 5 926 <5 ~8 927 <5 ~2 928 <5 10 929 <5 6 930 <5 ~14 931 <5 31 932 <5 2 933 <5 5 934 <5 27 935 <5 ~2 936 <5 7 937 <5 ~9 938 <5 43 939 <5 2 940 <5 33 941 <5 5 942 <5 11 943 <5 9 944 <5 5 945 <5 38 946 <5 37 947 <5 ~14 948 <5 25 949 <5 ~4 950 <5 ~1.27 951 <5 41 952 <5 45 953 <5 35 954 <5 27 955 <5 34 956 <5 8 957 <5 13 958 <5 ~6 959 <5 ~7 960 <5 ~2 961 <5 7 962 <5 43 963 ~4.99 62 964 ~4.96 41

Biological Example 2

Fatty Acid Synthase Keto-reductase Domain (FASN KR) Inhibition 10 μL assay buffer (100 mM KH₂PO₄ pH 7.5) was added to a 384-well clear plate (costar 3702). 0.3 μL compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO, 10 μL hFASN enzyme (full length, 300 ng, purified in house) and 360 μM NADPH (except in blank) were then added. Then, 10 μL 180 mM ethyl acetoacetate (Aldrich 688983) was added, mixed and immediately thereafter, the absorbance at 340 nm (T1) by Multiscan (Labsystems) was measured. After 20 minutes incubation at room temperature the plate was measured again (T2).

Enzymatic activity of FASN KR was measured as the oxidation of NADPH to NADP⁺ (a decrease in NADPH signal was observed at OD 340 nm,). The decrease in absorbance was calculated as (Absorbance before incubation T1)−(Absorbance following incubation T2).

Raw data generated by the instrument were normalized to % Controlmin values, which were calculated as:

% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and high control wells on the plate, after manual exclusion of outliers. A plot of Controlmin versus test compound concentration was fitted to a 4-parameter logistic curve using a non-linear least squares regression method. From the plot, an IC₅₀ (concentration at such 50% inhibition is achieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀), when IC₅₀ is expressed in molar units.

Representative compounds of the present invention were tested according to the procedure as described in Biological Example 2 above, with results as listed in Table 7, below.

TABLE 7 FASN Keto-reductase domain pIC₅₀ FASN Keto-reductase ID No. Domain pIC₅₀ 1 6.12 2 7.05 4 7.34 10 6.3 11 5.69 12 7.31 14 6.52 15 7.15 17 6.46 19 5.5 20 6.17 27 6.92 28 7.17 29 5.63 30 6.55 31 7.45 33 7.25 34 6.45 35 6.56 36 5.85 38 6.19 39 6.67 40 7.37 41 6.07 47 7.56 48 6.55 49 6.81 51 6.79 52 5.75 56 5.86 57 5.77 58 7.28 59 6.88 60 6.54 63 7.07 65 7.27 66 6.55 67 5.81 68 6.79 69 6.07 70 5.87 71 7.18 72 6.76 73 7.19 74 7.22 75 5.67 76 6.1 77 6.06 78 6.65 79 6.49 80 5.83 81 6.73 82 5.92 85 5.69 90 5.87 92 7.11 93 6.58 94 6.05 100 6.68 101 6.42 102 5.97 103 6.5 105 6.3 106 6.22 112 6.69 113 5.97 114 6.63 115 6.91 200 7.46 201 7.47 202 7.13 203 7.33 204 6.93 205 6.94 206 7.12 207 6.95 208 6.98 209 6.59 210 6.77 211 6.7 212 7.43 213 7.12 214 7.09 215 7.61 216 7.31 217 7.31 218 6.99 219 6.58 220 6.58 221 6.63 222 ~7.29 224 7.11 225 7.13 226 7.62 227 6.82 228 6.95 230 6.98 231 6.55 232 6.49 233 7.03 234 7.29 235 7.34 236 7.02 237 6.92 238 6.98 239 6.89 240 7.58 241 7.54 242 7.45 243 7.38 244 7.25 245 7.43 246 7.42 247 7.75 248 6.83 249 7.71 250 7.16 251 7.37 252 7.64 253 7.56 254 7.3 255 7.08 256 7.02 257 6.7 258 7.08 259 7.53 260 7.43 261 7.05 262 7.14 263 6.6 264 6.8 265 ~7.27 266 7.33 267 7.29 268 7.16 269 7.18 270 6.78 271 6.78 272 ~7.41 273 6.84 274 7.0 278 7.16 279 7.35 280 6.9 281 6.96 282 6.65 283 7.03 284 7.51 286 7.22 287 6.78 288 7.27 289 6.49 290 6.48 291 7.42 292 6.61 293 6.76 294 6.95 295 6.98 296 7.09 297 7.21 298 7.57 299 7.23 300 6.9 301 7.56 302 7.22 303 7.16 304 6.65 305 7.51 306 6.98 307 6.84 308 6.89 309 7.61 310 7.22 311 7.35 312 7.12 313 7.28 314 7.09 315 6.6 316 7.12 317 7.23 318 6.91 319 7.27 320 ~7.57 321 7.32 322 7.1 323 7.35 324 7.17 325 6.31 326 6.39 327 6.8 328 7.1 331 6.61 332 7.22 333 6.75 334 7.36 335 6.78 336 7.16 337 7.1 338 6.83 339 7.32 340 7.42 341 6.68 342 6.71 343 6.93 344 7.34 345 6.64 346 7.27 347 6.92 348 7.06 349 7.23 350 7.26 351 7.21 352 7.03 353 6.97 354 6.95 355 7.37 356 6.32 357 7.2 358 7.29 359 7.38 361 7.34 362 6.9 365 7.27 368 7.23 369 7.43 370 7.39 371 6.89 372 7.31 374 7.45 375 7.05 377 ~7.44 378 7.34 379 7.56 380 7.02 381 7.45 382 7.18 383 7.21 384 ~6.07 385 7.36 387 6.12 388 5.96 390 6.17 391 6.41 392 6.06 397 ~5.41 398 6.02 399 5.88 400 6.32 402 6.52 404 6.31 405 6.4 406 6.44 409 6.46 410 6.4 411 6.37 412 6.37 413 6.05 414 6.53 418 6.52 419 5.96 420 6.01 421 5.75 423 6.26 425 6.19 426 6.15 427 5.95 428 6.23 429 6.29 431 6.33 432 6.35 435 5.91 440 6.67 442 6.47 443 5.98 444 6.25 445 6.68 449 6.02 450 6.19 452 6.28 453 5.95 455 6.45 457 5.84 461 5.93 462 6.04 463 6.01 465 6.7 466 5.87 467 6.01 468 5.8 469 6.47 470 6.94 471 6.48 472 6.41 473 6.28 474 6.74 475 6.43 476 6.21 479 6.35 480 6.28 483 6.76 484 6.59 485 6.52 486 5.58 488 6.3 489 6.57 490 6.44 491 6.49 493 6.37 494 6.18 495 6.14 496 6.24 497 5.56 498 6.54 499 6.32 502 5.67 507 5.44 510 5.27 511 5.5 512 5.51 515 6.36 517 5.82 519 6.41 520 6.2 521 6.17 523 5.83 526 5.66 528 6.21 529 6.81 530 5.53 531 6.27 534 5.86 536 5.45 537 6.37 538 6.48 541 6.47 542 5.79 543 6.32 544 6.14 545 6.59 546 6.22 547 6.17 548 6.78 554 6.57 557 6.37 558 6.15 562 5.86 566 6.11 576 6.17 578 5.81 579 5.34 580 6.22 581 6.2 582 5.92 584 6.77 585 6.79 586 5.78 588 5.93 591 5.98 594 5.97 596 6.23 598 6.51 599 6.56 600 5.92 601 6.3 602 5.81 604 5.06 606 5.84 607 6.27 608 5.99 609 6.17 613 6.64 614 6.51 615 5.98 616 5.81 617 6.2 618 5.95 619 6.42 621 6.29 622 5.6 623 6.63 627 6.9 628 6.32 635 5.87 637 6.06 638 6.0 639 5.84 641 6.45 642 6.11 644 5.84 645 6.17 647 5.86 649 6.43 652 6.46 655 6.39 657 6.18 661 6.88 662 6.21 663 6.56 665 6.2 667 6.47 669 6.27 672 6.26 674 5.5 676 6.22 678 6.08 680 6.65 681 5.86 682 6.74 685 5.79 686 6.17 688 6.28 690 5.99 692 5.49 698 6.34 699 5.27 700 6.08 701 5.41 704 5.18 714 5.82 715 5.26 716 5.98 717 5.7 720 5.19 725 6.19 727 5.96 728 6.5 729 6.09 730 6.45 733 6.27 735 6.07 737 5.65 739 6.29 741 6.27 742 6.45 743 5.8 744 6.6 745 6.8 746 5.97 747 6.89 748 6.28 749 6.22 750 5.94 751 6.78 752 5.98 753 6.19 755 6.2 757 6.0 762 6.12 765 6.08 845 7.6 872 7.37 873 7.39 874 7.39 875 7.54 876 7.44 877 7.13 878 7.22 879 7.26 880 6.95 881 6.5 882 6.53 883 5.98 884 6.13 885 6.31

Biological Example 3 A2780 Ovarian Cell Proliferation Assay in Lipid Reduced Medium, With and Without palmitate

The biological assays described below correspond to comparative assays for ovarian cell proliferatioin. The assay procedure described below which includes addition of added palmitate correspond to the control relative to the assay procedure which does not include addition of the palmitate. Compounds active in the absence of palmitate would not be expected to be active in the control.

With Palmitate:

2500 cells were seeded in a 96-well clear well plate in 200 μL RPM11640 with 10% Fetal Calf Serum (Hyclone), and incubated at 37° C., 5% CO₂. Blanks were wells without cells. The next day the culture medium was aspirated and replaced by 160 μL culture medium with 10% Lipid-Reduced Serum (LRS, Hyclone). 20 μL test compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO dilution followed by 20 μL palmitate-BSA solution were added to a final concentrations of 0.2% DMSO, 25 μM palmitate (Sigma, P0500, 10 mM stock solution in ethanol) 0.2% fatty-acid-free BSA, 0.25% ethanol. After 96 h incubation, an MTT assay was performed. The absorbance was measured at 544 nm on a SPECTRAMAX brand microplate reader (Molecular Devices).

A best fit curve was fitted by a minimum sum of squares method, plotting Control_(min) versus test compound concentration. From the plot, an IC₅₀ (concentration at such 50% inhibition is achieved) was calculated. pIC₅₀ values, presented in the Table below, were calculated as −log(IC₅₀).

Without Palmitate:

2500 cells were seeded in a 96-well clear well plate in 200 μL RPM11640 with 10% Fetal Calf Serum (Hyclone), and incubated at 37° C., 5% CO₂. Blanks were wells without cells. The next day the culture medium was aspirated and replaced by 160 μL culture medium with 10% Lipid-Reduced Serum (LRS, Hyclone). 20 μL test compound (at concentrations of 30 μM, 10 μM, 3 μM, 1 μM, 0.30 μM, 0.10 μM, 0.03 μM and 0.01 μM)/DMSO dilution followed by 20 μL ethanol-BSA solution were added to a final concentrations of 0.2% DMSO, 0.2% fatty-acid-free BSA, 0.25% ethanol. After 96 h incubation an MTT assay was performed. The absorbance was measured at 544 nm on a SPECTRAMAX brand microplate reader (Molecular Devices).

Raw data generated by the instrument were normalized to % Controlmin values, which were calculated as:

% Controlmin=100*(x−mLC)/(mHC−mLC)

where mLC and mHC were the means of the low control wells and high control wells on the plate, after manual exclusion of outliers. A plot of Controlmin versus test compound concentration was fitted to a 4-parameter logistic curve using a non-linear least squares regression method. From the plot, an IC₅₀ (concentration at such 50% inhibition is achieved) was calculated. pIC₅₀ values were calculated as −log(IC₅₀), when IC₅₀ is expressed in molar units.

Representative compounds of the present invention were tested according to the procedure as described in Biological Example 3 above, with results as listed in Table 8, below. Where a compound was tested more than once, the IC₅₀ value listed below represents the mean of the three measurements. Wherein the results listed below, the pIC₅₀ value is preceded with a “˜”, the “˜” the “˜” indicates that the standard error of the pIC₅₀ value, as estimated by the non-linear regression algorithm, is larger than 0.5. This corresponds to a factor of uncertainly on the IC₅₀ that is larger than square root of 10 (>3.162).

TABLE 8 pIC50 Ovarian Cell, Reduced Lipid Medium With and Without Palmitate pIC₅₀ A2780 Ovarian pIC₅₀ A2780 Ovarian ID No. Cell, With Palmitate Cell, Without Palmitate 1 <5 5.95 2 <5 6.01 4 5.29 7.23 10 <5 6.06 11 <5 ~5.52 12 5.42 ~7.44 14 <5 5.91 15 <5 ~7.2 17 <5 6.4 19 <5.21 5.33 20 5.09 6.19 27 <5 6.6 28 <5 6.88 29 <5 5.47 30 <5 6.42 31 <5 7.54 33 <5 6.6 34 <5 6.11 35 <5 6.32 36 <5 5.46 38 <5 5.92 39 <5 6.48 40 <5 7.14 41 <5 5.92 47 <5 8.11 48 <5 6.74 49 <5 6.48 51 <5 6.91 52 <5 5.73 56 5.22 5.8 57 <5 5.6 58 <5 6.47 59 <5 7.02 60 <5 6.58 63 <5 7.12 64 <5 6.2 65 <5 ~7.88 66 <5 5.96 67 <5 5.79 68 <5 6.47 69 <5 5.94 70 <5 ~5.62 71 <5 7.44 72 <5 5.86 73 <5 ~7.54 74 <5 8.06 75 <5 5.23 76 <5 6.29 77 <5 6.18 78 <5 6.83 79 <5 6.84 80 <5 5.64 81 <5.21 6.99 82 <5 5.43 85 <5 ~5.54 90 <5 5.2 92 <5 7.34 93 <5 ~5.68 94 <5 ~5.67 100 <5 6.11 101 <5 5.77 102 <5 5.64 103 <5 6.07 105 <5 6.02 106 <5 6.13 112 <5 5.99 113 <5 ~5.75 114 <5 ~6.08 115 <5 ~7.21 116 ~5.52 7.45 117 5.04 ~5.62 118 <5 5.78 119 4.96 ~5.65 120 5.3 ~6.12 121 <5 5.66 122 ~5 6.63 124 <5 ~6.54 126 <5 <5 127 5.12 6.03 133 <5 ~5.5 134 <5 5.35 137 ~5.22 ~6.07 200 <5 ~8.41 201 ~5.46 ~8.36 202 <5 7.23 203 <5 ~8.34 204 <5 ~7.39 205 <5 7.44 206 <5 ~7.98 207 <5 7.22 208 5.22 ~7.14 209 <5 5.73 210 <5 7.28 211 <5 ~6.15 212 <5 8.14 213 <5 6.94 214 <5 ~7.19 215 <5 7.69 216 <5 7.2 217 <5 7.52 218 <5 7.07 219 5.93 7.17 220 <5 6.47 221 5.16 7.33 222 ~5.61 8.21 223 5.48 ~7.7 224 ~5 8.11 225 5.28 7.6 226 <5 8.63 227 <5 7.88 228 <5 7.74 230 <5 6.26 231 <5.21 5.6 232 <5.21 5.62 233 <5 6.04 234 <5 ~7.54 235 <5 8.0 236 <5 ~7.05 237 <5 7.45 238 <5 7.37 239 <5 7.22 240 <5.21 6.7 241 <5 ~7.12 242 <5 ~6.14 243 <5.21 6.19 244 <5 ~5.65 245 <5 5.81 246 <5 ~8.3 247 <5 8.3 248 <5 6.29 249 <5 ~8.26 250 <5 6.52 251 <5 7.14 252 <5 ~7.11 253 <5 7.92 254 <5 6.36 255 <5 ~6.01 256 <5 6.08 258 <5 ~7.95 259 <5 6.98 260 <5 ~7.15 261 <5 8.18 262 5.22 7.11 263 <5 6.92 264 <5 7.13 265 <5 ~8.54 266 5.87 ~8.66 267 <5 8.77 268 <5 ~7.35 269 5.37 ~8.43 270 ~5.26 ~7.56 271 <5 ~7.13 272 <5 ~8.14 273 5.1 ~7.68 274 5.14 ~7.62 278 <5 ~6.16 279 <5 6.39 280 <5 ~5.71 281 <5.21 ~6.09 282 <5 ~5.68 283 <5 ~5.73 284 <5 ~7.63 286 <5 ~7.67 287 <5 ~6.55 288 <5 ~6.97 289 <5 5.95 290 <5 ~5.71 291 <5 7.34 292 <5 6.9 293 <5 7.06 294 <5 ~5.73 295 <5 6.2 296 <5 ~5.68 297 <5 7.6 298 <5 7.23 299 <5 7.51 300 <5 7.13 301 <5 7.83 302 <5 7.88 303 <5.21 7.54 304 <5 7.07 305 <5 7.39 306 <5 7.75 307 <5 7.04 308 <5 6.84 309 <5 8.21 310 <5.21 6.23 311 <5 ~6.64 313 5.06 7.27 316 <5 ~7.8 317 <5 7.61 318 <5 ~7.15 319 <5 ~7.87 320 5.19 7.6 321 5.36 7.75 322 <5 7.83 323 <5 ~8.54 324 <5 7.71 325 <5 ~7.31 326 5.04 ~7.92 327 5.09 7.98 328 5 8.29 329 5.51 7.85 330 ~5.21 7.49 331 5.25 7.16 332 5.38 7.91 333 <5 ~7.48 334 5.16 7.62 335 <5 6.86 336 <5 7.7 337 5.16 7.42 338 ~5.37 7.66 339 ~5.55 7.54 340 5.22 7.81 341 <5.21 6.88 342 <5 5.73 346 <5 ~7.77 347 <5 ~7.3 348 <5 7.54 349 <5 ~7.51 350 <5 ~7.55 351 5.07 7.55 352 5.52 ~6.91 353 5.22 6.61 354 <5 7.51 355 <5 7.52 356 <5 ~6.79 357 <5 7.65 358 <5 8.5 359 <5.21 8.09 361 <5 ~8.44 362 <5 ~7.37 363 ~5.82 ~8.19 364 6.64 ~8.53 365 ~5 8.19 366 6.25 ~8.25 368 5.35 7.67 369 5.68 8.37 370 <5 ~8.62 371 5.09 7.14 372 <5 8.3 374 <5 8.0 375 <5 7.14 377 <5 7.64 378 <5 ~8.29 379 <5 ~8.97 380 <5 6.88 381 <5 ~8.6 382 <5 ~8.17 383 ~5.33 7.98 384 5.28 7.14 385 ~5.59 ~8.44 387 <5 ~5.49 388 <5 ~5.61 390 <5 ~5.58 391 <5 5.93 392 <5 5.6 397 <5 5.81 398 <5 ~5.64 399 <5.21 <5.21 400 <5.21 6.64 402 <5 6.76 404 <5 5.96 405 <5 6.32 406 <5 5.22 409 <5 5.68 410 <5 6.27 411 <5 6.9 412 <5 5.79 413 5.14 ~6.17 414 <5 ~6.7 418 <5 ~5.67 419 <5 6.19 420 <5 ~5.68 421 <5 5.94 423 <5 5.89 425 <5 ~5.16 426 <5 5.63 427 <5 6.08 428 <5 ~5.96 429 <5 6.38 431 <5 6.69 432 <5.21 5.82 435 <5 ~6.03 440 <5 7.02 442 <5 6.59 443 <5 6.1 444 <5 ~6.68 445 <5 7.17 449 <5 ~5.02 450 <5 ~6.21 452 <5 6.2 453 <5 5.67 455 <5 ~6.05 457 <5.21 5.9 461 <5 ~6.37 462 <5 5.73 463 <5 ~5.42 465 <5 6.74 466 <5 ~5.57 467 <5 6.12 468 <5 6.18 469 <5 7.13 470 <5 ~6.03 471 <5 6.38 472 <5 6.63 473 <5 ~6.56 474 <5 6.7 475 <5 6.09 476 <5 ~5.69 479 <5 6.16 480 <5 ~6.59 483 <5 7.32 484 <5 7.02 485 <5 ~6.91 486 <5 ~5.66 488 <5 6.52 489 <5 6.83 490 <5 7.03 491 <5 7.14 493 <5 ~6.68 494 <5 6.16 495 <5 6.56 496 <5 6.68 512 <5 6.0 518 ~5.39 ~5.4 520 <5 6.41 521 <5 ~6.47 522 <5 5.54 523 <5 6.17 524 <5 5.31 525 <5 5.31 526 <5 ~5.99 527 <5 ~5.71 528 <5 ~6.4 529 <5 ~7.08 530 <5 6.11 531 <5 6.83 532 <5 <5 533 <5 <5 534 <5 6.11 535 5.11 5.18 536 <5 6.02 537 <5 6.58 538 ~5 6.88 539 <5 <5 540 5.03 5.35 541 <5 6.55 542 <5 6.08 543 <5 6.85 544 5.79 7.28 545 <5 7.04 546 <5 ~6.71 547 5.23 ~6.76 548 5.21 ~6.53 549 <5 5.42 550 ~5 5.46 551 <5 ~5 552 <5 5.77 553 <5 5.56 554 5.11 ~6.84 555 <5 ~5.29 556 <5 5.23 557 5.32 6.7 558 5.2 ~6.25 559 <5 5.03 560 <5 ~5.12 561 <5 <5 562 <5 6.02 563 <5 5.5 564 <5 6.28 566 <5 6.53 568 5.62 7.33 569 5.66 6.69 570 <5 ~5.28 571 <5 6.01 572 <5 7.28 573 5.86 7.27 574 5.24 6.06 575 <5 ~5.1 576 <5 6.54 577 <5 5.61 578 <5 6.48 579 <5 5.96 580 <5 7.25 581 5.37 ~6.7 582 <5 ~6.2 583 <5 5.59 584 5.18 7.2 585 <5 7.08 586 <5 ~6.07 587 <5 ~5.07 588 <5 ~6.17 589 <5 5.25 590 <5 5.48 591 <5 ~6.46 592 <5 5.28 593 5.02 5.17 594 <5 6.21 595 5.18 5.49 596 5.2 6.34 597 5.36 5.44 598 <5 6.7 599 5.26 6.84 600 <5 ~6.22 601 5.41 6.66 602 5.21 6.42 603 <5 ~5.48 604 ~5 5.63 605 5.2 5.32 606 <5 5.91 607 <5 6.19 608 <5 6.43 609 <5 ~6.58 610 5.34 5.54 611 <5 <5 612 <5 5.42 613 <5 6.97 614 <5 6.77 615 <5 6.3 616 <5 5.74 617 <5 6.61 618 <5 6.1 619 <5 ~6.65 620 <5 ~5.32 621 5.21 6.15 622 <5 5.66 623 5.29 ~7.49 624 5.18 5.84 627 <5 7.92 628 <5 7.18 629 <5 5.11 630 <5 5.39 631 <5 5.23 632 <5 ~5.62 633 <5 5.28 634 <5 5.7 635 <5 6.89 636 <5 ~5.23 637 <5 7.07 638 <5 ~6.71 639 <5 ~6.44 640 <5 5.08 641 <5 ~5.65 642 <5 ~5.42 643 ~5 ~6.17 644 <5 6.79 645 <5 ~5.69 646 <5 5.61 647 <5 5.71 648 <5 5.6 649 5.13 6.7 650 <5 5.31 651 <5 5.56 652 <5.21 6.76 653 <5 5.38 654 <5 5.66 661 <5 7.37 662 <5 6.34 664 <5 ~5.54 665 <5 6.26 667 <5 ~6 672 <5 ~6.39 678 <5 6.17 681 <5 6.1 682 <5 6.93 683 <5 <5 685 <5 5.91 690 <5 6.15 698 <5 6.42 700 <5 6.33 701 <5 6.05 714 <5 6.03 716 <5 6.29 717 <5 5.79 729 <5 5.89 741 <5 ~5.6 742 ~5.22 ~5.6 743 <5 5.68 744 <5 ~6.67 745 <5 7.02 746 <5 ~5.73 747 <5 ~7.13 748 <5 ~6.65 749 <5 5.81 750 <5 6.17 751 <5 7.05 752 <5 5.79 753 <5 ~6.61 755 <5.21 ~6.5 757 <5 6.15 762 <5 ~6.01 765 <5 5.66 775 <5 <5 776 <5 <5 777 <5 5.02 784 <5 5.23 785 ~5.21 5.41 786 5.23 5.17 787 <5 5.03 788 <5 <5 789 <5 <5 790 <5 <5 791 <5.21 <5.21 792 <5 <5 793 <5 <5 794 <5 <5 795 <5 <5 836 <5.52 6.43 837 <5.52 5.91 840 <5.52 <5.52 842 <5.52 <5.52 844 <5.52 <5.52 845 <5 7.96 872 ~5.1 8.57 873 <5 7.2 874 <5 7.68 875 <5 7.87 876 <5 6.64 877 <5 7.67 878 <5 ~7.03 879 <5 7.6 880 <5 7.18 881 <5 6.62 882 <5 ~7.05 883 <5 ~5.61 884 <5 ~5.67 885 <5 ~5.65 891 <5 <5 896 <5 <5 897 <5 <5 898 <5 <5 899 <5 <5 900 <5 <5 918 <5 <5 922 <5 <5 923 <5 <5 937 <5 <5 938 <5 5.1 939 <5 <5 940 <5 <5 943 <5 <5 957 <5 <5 963 <5 <5

Biological Example 4 Example 4a In Vitro LNCaP Vancouver Prostate Cell Proliferation Assay in Lipid Reduced Medium

LNCaP-Vancouver prostate cells were obtained from the Vancouver Prostate Cancer Centre. Cells were maintained in RPMI-1640, 10% Fetal Calf Serum (FCS, Hyclone), 2 mM glutamine and 50 μg/ml Gentamicin.

For the proliferation experiment 1500 LNCaP-Vancouver cells per well were seeded in a 384-well black with clear bottom plate (costar 3712BC) in 40 μl RPMI-1640, 10% Lipid reduced serum (LRS, Hyclone), 50 μg/ml Gentamicin and 2 mM Glutamine and incubated at 37° C., 5% CO₂. The next day 10 μl of test compound/DMSO diluted in medium was added (3E-5M, 1E-5M, 3E-6M, 1E-6M, 3E-7M, 1E-7M, 3E-8M, 1E-8M final concentration). Compounds were tested in duplicate. After 96 h incubation at 37° C., 5% CO₂25 μl ATP-glow mix was added. The plate was incubated for 30 min at 37° C. and luminescence was measured with the Envision.

Example 4b In Vitro PC-3M-Luc-C6 Prostate Cell Proliferation Assay in Lipid Reduced Medium

PC-3M-Luc-C6 prostate cells were obtained from Xenogen Corporation. Cells were maintained in MEM supplement end with 10% Fetal Calf Serum (FCS, Hyclone), 2 mM glutamine, 1 mM sodium pyruvate, 1% BME vitamins (available from for example, Sigma Aldrich), 0.1 mM non Essential Amino Acid and 50 μg/ml Gentamicin. The cells were passaged twice a week.

1000 PC-3M-Luc-C6 prostate cells (Xenogen) were seeded in a 384-well black with clear bottom plate (costar 3712BC) in 40 μl MEM, 10% LRS (Hyclo ne), 50 μg/ml Gentamicin, 2 mM Glutamine, 1 mM Sodium pyruvaat, 1% BME vitamins and 0.1 mM non Essential Amino Acid and incubated at 37° C., 5% CO₂. The next day 10 μl test compound/DMSO diluted in medium was added (3E-5M, 1E-5M, 3E-6M, 1E-6M, 3E-7M, 1E-7M, 3E-8M, 1E-8M final concentration). Compounds were tested in duplicate. After 96 h incubation at 37° C., 5% CO₂ 25 μl ATP-glow mix was added. The plate was incubated for 30 min at 37° C. and luminescence was measured with the Envision.

Analysis: Determination of pIC50 values

pIC₅₀ values were calculated as follows. Raw data generated by the instruments were normalized to % Control_(min) values, which were calculated as:

% Control_(min)=100*(x−mLC)/(mHC−mLC),

where mLC and mHC are the means of the low control wells and high control wells on the plate, after manual exclusion of outliers. The relation between the % Control_(min) values and concentration was fitted to a 4-parameter logistic curve using a non-linear least squares regression method to determine the pIC₅₀ value. Outlying data points were excluded manually to get a correct fit. The pIC₅₀ corresponds to −log 10(IC₅₀), if the IC₅₀ is expressed in molar units (http://www.ncbi.nlm.nih.gov/books/NBK91994). The IC₅₀ parameter was always determined by non-linear regression, but one or more of the other parameters may have been held fixed on a relevant input value, such as 0 for the bottom values.

For dose response curves with FASN inhibitors in LNCaP-Vancouver or PC-3M-Luc-C6 cells the curves bottom out around 30 to 40% of the control value. A standard fit PL2, forcing the lower bound to this level was used. For those test compounds which did not exhibit FASN related toxicities (but other non-target related cellular toxicity), the % control value may go to 0, and curve fit was calculated using 0% as lower bound.

Representative compounds of the present invention were tested according to the procedure as described in Biological Example 4a and 4b above, with results as listed in Table 9, below. Where a compound was tested more than once, the pIC₅₀ value listed below represents the mean of the measurements. Wherein the results listed below, the pIC₅₀ value is preceded with a “˜”, the “˜” the “˜” indicates that the standard error of the pIC₅₀ value, as estimated by the non-linear regression algorithm, is larger than 0.5. This corresponds to a factor of uncertainly on the pIC₅₀ that is larger than square root of 10 (>3.162).

TABLE 9 pIC50 Prostate Cell Proliferation, Reduced Lipid Medium pIC₅₀ LNCaP_Vancouver pIC₅₀ PC-3M-Luc- ID No. prostate cell C6 prostate cell 2 ~5.71 ~6.18 39 5.98 6.82 49 6.04 6.66 59 6.58 7.0 65 7.18 ~7.61 200 ~7.47 8.19 201 7.68 ~8.18 202 6.26 ~7.02 203 7.67 8.25 204 6.39 7.29 205 6.99 7.27 206 7.0 7.72 207 6.29 ~7.17 208 6.93 7.36 209 5.38 ~6.11 212 6.96 7.74 213 6.45 ~6.95 214 6.44 7.18 215 7.15 7.8 216 6.79 ~7.27 217 6.75 7.3 218 6.38 7.14 219 6.52 6.9 220 5.97 ~6.54 221 ~6.42 6.88 222 7.33 8.03 223 6.62 7.22 224 7.25 7.9 225 6.8 7.57 226 7.66 ~8.23 227 6.45 7.26 228 6.12 7.01 230 5.91 6.42 231 5.66 ~5.79 232 5.74 5.97 233 5.77 6.24 234 6.61 7.63 236 6.19 7.29 237 6.2 ~7.13 238 6.61 7.15 239 6.09 6.87 240 6.27 ~6.78 241 6.78 ~7.25 242 ~5.8 ~6.19 243 6.08 ~6.62 244 5.74 ~5.85 245 ~5.77 ~6.19 246 7.81 8.32 247 7.63 8.14 248 6.32 6.58 249 7.78 8.38 250 6.16 6.63 251 6.86 ~7.38 252 6.6 7.25 253 7.19 7.85 254 5.86 6.65 255 5.95 ~6.28 256 5.62 ~6.38 257 6.58 7.15 258 7.5 7.84 259 6.35 7.17 260 7.07 7.43 261 ~6.99 7.67 262 6.53 ~6.93 263 6.95 264 6.3 7.35 265 7.86 ~8.15 266 7.82 8.33 267 7.91 ~8.51 268 6.54 7.23 269 7.55 ~8.08 270 6.71 7.46 271 6.38 7.01 272 7.31 7.97 273 6.45 7.17 274 6.47 7.33 282 ~5.67 ~5.77 284 7.42 7.74 286 6.91 7.6 288 6.27 7.11 290 ~5.67 ~5.93 291 6.53 ~7.37 292 6.16 6.75 293 ~6.29 ~6.85 294 5.69 ~6.06 295 5.89 ~6.24 296 5.44 ~5.91 297 6.19 ~7.52 298 6.21 7.18 299 6.63 7.41 300 5.72 6.91 301 6.56 7.92 302 6.36 7.78 303 ~6.04 7.4 304 5.9 7.14 305 6.58 7.54 306 6.29 7.77 307 6.18 6.99 308 6.32 7.0 309 7.5 8.13 310 6.09 ~6.49 311 6.52 6.97 312 6.91 ~7.28 313 6.81 ~7.28 314 6.51 7.24 315 6.2 6.91 316 6.99 7.71 317 6.59 7.29 318 5.84 7.28 319 6.95 7.73 320 6.6 7.3 321 6.74 7.3 322 6.82 ~7.46 323 7.48 8.08 324 6.8 ~7.52 325 6.44 7.08 326 6.77 7.31 327 6.86 7.46 328 7.27 7.79 331 6.21 6.83 332 6.97 7.91 333 6.27 ~6.47 334 6.79 7.43 335 6.22 ~6.94 336 6.98 337 7.1 7.69 338 6.9 7.72 339 6.49 7.5 340 7.03 7.74 341 6.28 6.9 342 5.79 ~6.05 343 6.62 7.09 344 6.85 ~7.49 345 5.92 6.25 346 7.36 7.65 347 6.15 ~7.05 348 6.55 7.39 349 6.86 7.47 350 7.09 7.65 351 7.24 7.86 352 6.25 6.79 353 5.94 6.36 354 6.61 7.45 355 6.24 7.23 356 5.83 ~6.49 357 6.43 7.6 358 7.11 7.83 359 ~7.1 8.08 361 ~7.89 8.49 362 ~6.53 ~7.25 365 7.25 8.12 368 6.67 7.54 369 7.34 8.0 370 7.69 ~8.41 371 6.31 7.26 372 7.12 7.88 374 7.06 7.69 375 6.34 7.11 377 7.09 7.55 378 7.13 7.98 379 8.3 ~8.61 380 5.94 6.51 381 7.98 8.72 382 7.26 7.57 383 7.3 ~7.74 384 6.08 6.78 385 7.73 ~8.32 390 5.56 5.83 391 5.77 6.14 392 ~5.77 5.79 397 5.52 5.97 398 5.63 5.76 399 <5.52 <5.52 400 5.92 6.67 402 5.76 6.76 405 5.64 6.34 406 5.15 5.73 409 5.66 5.93 410 6.01 6.35 411 6.28 6.79 412 6.34 6.24 413 6.35 6.32 414 5.94 6.75 418 ~5.6 5.8 419 5.39 6.11 420 5.19 5.78 421 5.89 5.98 423 5.59 5.87 425 5.5 5.66 426 5.63 5.76 427 5.58 6.07 428 5.55 6.1 429 5.88 6.41 432 5.69 6.06 435 5.46 5.91 440 5.94 6.63 442 5.71 6.29 443 5.64 6.07 444 5.74 6.38 445 5.93 6.63 449 <5 5.62 450 5.63 6.1 452 5.69 6.26 453 5.53 5.79 455 5.67 ~6.16 457 <5.52 5.66 461 ~5.6 ~6.22 462 5.63 5.93 463 5.14 5.72 465 6.28 6.73 466 5.42 5.73 467 5.54 6.11 468 5.69 6.26 469 6.54 7.23 470 5.83 ~6.2 471 5.89 6.54 472 5.75 6.88 473 5.66 6.56 474 6.0 6.15 475 5.48 6.18 476 5.43 ~5.67 479 6.03 6.52 480 5.94 6.74 483 6.42 ~7.04 484 6.26 6.82 485 6.2 6.67 486 5.35 ~5.55 488 5.81 6.24 489 6.15 ~6.6 490 5.98 ~6.69 491 6.0 ~6.75 493 5.9 6.8 494 5.33 6.05 495 ~5.49 ~6.23 496 5.76 ~6.45 497 5.27 6.32 498 5.61 6.63 499 5.37 6.34 502 5.38 5.93 507 5.22 ~5.93 510 5.32 ~5.42 511 5.33 ~6.05 512 5.4 5.88 515 5.67 6.25 517 ~5.28 5.9 519 5.57 6.26 520 5.59 6.3 521 5.72 6.22 523 5.49 5.93 526 5.23 5.83 528 5.63 6.3 529 6.14 ~7.08 530 5.29 5.91 531 5.87 6.52 534 ~5.25 6.0 536 ~5.12 ~5.51 537 5.88 6.21 538 5.71 ~6.69 541 ~5.99 6.51 542 5.52 5.35 543 5.7 6.59 544 6.11 6.85 545 6.57 6.9 546 5.82 ~6.51 547 6.0 6.27 548 5.96 6.41 554 6.19 ~6.76 557 5.86 6.37 558 5.6 6.14 562 5.51 5.79 566 5.81 6.24 576 5.67 6.17 578 5.3 6.06 579 5.34 5.7 580 6.12 6.73 581 ~6.53 582 5.49 6.1 584 6.19 7.08 585 7.0 586 5.99 588 ~6.02 591 6.43 594 5.72 ~6.23 596 5.73 ~6.12 598 5.63 ~6.45 599 6.04 6.98 600 5.65 6.3 601 5.99 6.5 602 5.83 6.16 604 <5 5.38 606 5.62 5.95 607 5.96 6.75 608 5.73 ~6.58 609 5.32 6.18 613 6.07 7.01 614 5.87 6.42 615 5.49 ~5.63 616 5.5 <5 617 5.59 6.19 618 5.46 ~5.59 619 5.49 6.2 621 5.67 6.36 622 <5 5.66 623 6.25 6.91 627 ~6.89 7.32 628 6.14 6.79 635 5.99 6.45 637 5.74 ~6.63 638 5.77 6.32 639 5.63 6.1 641 5.34 ~6.25 642 5.21 ~5.67 643 5.52 6.01 644 5.55 6.4 645 5.46 5.76 647 5.29 5.76 649 5.76 6.36 652 5.92 6.41 655 ~5.6 ~6.63 657 5.42 6.23 661 6.72 ~7.1 662 5.54 6.15 663 6.26 6.93 665 5.91 6.1 667 5.75 ~5.81 669 5.55 ~6.09 672 5.58 ~6.26 674 ~5.31 ~6.09 676 5.75 6.3 678 5.48 6.05 680 6.47 6.97 681 5.31 5.86 682 6.0 6.66 685 5.52 5.93 686 5.42 5.96 688 5.53 6.08 690 5.63 5.88 692 5.34 5.8 698 5.58 6.24 699 <5 5.29 700 5.47 6.0 701 5.34 5.9 704 5.16 ~5.24 714 5.28 6.1 715 <5 5.3 716 5.26 5.97 717 5.3 5.77 720 5.04 5.33 725 5.78 6.31 727 5.62 6.24 728 6.28 6.82 729 5.06 5.84 730 ~6.39 7.01 733 5.48 5.89 735 5.42 ~6.04 737 ~5.43 6.15 739 5.42 ~6.06 741 5.56 ~5.79 742 ~5.35 ~5.76 744 6.07 6.74 745 6.07 6.74 746 ~5.41 ~5.78 747 6.2 7.24 748 5.52 6.24 749 5.64 6.12 750 5.5 6.23 751 6.14 6.69 752 5.4 5.72 762 5.41 6.09 765 5.05 5.68 872 7.62 8.32 873 6.58 7.46 875 7.06 7.98 876 6.21 6.92 877 ~6.39 7.34 879 6.42 7.51 880 6.19 6.93 881 5.88 6.73 884 5.52 ~5.74 885 <5 ~5.58

Biological Example 5 ¹⁴C-Acetate Incorporation in HEPG2 Liver Cells

HepG2 liver cells are obtained from the American Type Culture Collection. Cells are seeded in a 24-well plate at 7.10⁵ cells/well in 400 μL MEM with 10% FCS (Hyclone). 100 μL of test compound dilution (25 μM to 5 μM final) is added and plates are incubated for 4 hours at 37° C. in 5% CO₂. 50 μL of ¹⁴C-acetic acid (Acetic acid, sodium salt (1,2-14C): Amersham CFA13; 50-62 mCi/mMol, 200 μCi/ml (7.4 mBq/ml)) diluted 1/50 in medium is added and plates are incubated for another 2 h at 37° C. in 5% CO₂. Medium is aspirated, and lipids are extracted from the cells by 3 rounds of chloroform:methanol:MgSO₄ mixture and centrifugation steps (2 min at 10000 rpm). Each time the upper layer is removed. Finally the remaining organic layer is evaporated under nitrogen gas, the pellet are dissolved in 500 μL heptanes and in 3 ml of scintillation fluid added to scintillation tubes. Incorporated ¹⁴C-labelled is counted in a Pachard, Tri-Carb Liquid scintillation counter, (2 minutes)

Biological Example 6 Analysis of Intact Phospholipid Species by Electrospray Ionization Tandem Mass Spectrometry

PC-3 prostate and A2780 ovarian cells are obtained from the American Type Culture Collection. Cells are cultured in HamF12 or RPMI 1640 respectively, supplemented with 10% FCS (Invitrogen). Palmitic acid (Sigma) is complexed to fatty acid-free bovine serum albumin (Invitrogen). Cells are cultured for 72 hours in the presence or absence of test compound (10 μM to 0.1 μM). Xenografts are collected after 21 days treatment with or without compound (100-10 mg/kg).

Tissue or cells are homogenized in 1 N HCl/CH₃OH (1:8, v/v). CHCl₃, 200 μg/mL of the antioxidant 2,6-di-tert-butyl-4-methylphenol (Sigma; ref. 29), and lipid standards are added. The organic fractions are evaporated and reconstituted in CH₃OH/CHCl₃/NH₄OH (90:10:1.25, v/v/v). Phospholipids are analyzed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a hybrid quadrupole linear ion trap mass spectrometer (4000 QTRAP system, Applied Biosystems) equipped with a robotic nanoflow/ion source (Advion Biosciences). The collision energy is varied as follows: prec 184, 50 eV; nI 141, 35 eV; nI 87, −40 eV; prec 241, −55 eV. The system is operated in the multiple reaction monitoring (MRM) mode for quantification of individual species. Typically, a 3-minute period of signal averaging is used for each spectrum. Data are corrected for ¹³C isotope effects if the contribution is >10%. Corrected data were presented as heat maps using the HeatMap Builder software (Clifton Watt, Stanford University).

Biological Example 7 In Vivo Xenograft Assay Animals:

Male NMRI-nude mice (obtained from Janvier) are used for the study. Mice with an initial weight of approximately 20 to 25 g are obtained. The animals are habituated for one week prior to any experimental protocols/procedures being performed.

All animals are maintained under SPF “full barrier” conditions with free access to food and water. Mice are group housed under a 12-h light:dark cycle (lights on at 06:00 h) at a temperature of 19 to 22° C. and 35 to 40% humidity in Techniplast type-3 IVC cages. Mice are fed a standard Laboratory chow. All experiments are carried out in accordance with the European Communities Council Directives (86/609/EEC) and are approved by the local ethical committee.

Prostate Tumor Cells:

The human PC-3 prostate tumor cells are cultured at 37° C. in a humidified atmosphere (5% CO₂, 95% air), in F12-Ham medium supplemented with 2 mM Sodium Pyruvate, 50 μg/ml Gentamycin, 1.5 g/l Sodium Bicarbonate, 0.1 mM Non Essential Amino Acids and 10% fetal bovine calf serum. Cells are maintained as cell monolayer cultures, passaged twice weekly at 3×10⁶ cells per T175 flask, according to the following procedure. Cells are washed with PBS (w/o Mg²⁺, Ca²⁺), before addition of trypsin-EDTA to the culture flasks. After detachment of cells, the trypsin-EDTA is inactivated by addition of complete medium. The cell suspension is then transferred to 50 ml Falcon tube and centrifuged for 3 min at 1200 rpm. Medium is aspirated, with the cells being re-suspended in an appropriate volume of complete medium. The cells are counted in a haemocytometer and their viability is assessed by 0.25% trypan blue exclusion. An appropriate volume of cell suspension is then added to either a new T175 culture flask(s) or roller bottle containing fresh medium. For large scale-up growth of PC3 prostate tumor cells, an appropriate number of roller bottles are seeded with 1.2×10⁷ cells 1 week prior to inoculation of the mice. The medium is changed twice during this period, with the last change being the day prior to cell injection. Cells are collected as described above, with the exception that after centrifugation, the cells are re-suspended in cold (4° C.) serum free medium at 5×10⁷ cells/ml.

Experimental Design:

Human PC-3 prostate tumor cells are injected directly into the inguinal region of the male NMRI Nude mice (1×10⁷ cells/200 μl/animal) on day 0. Approximately 35 days after inoculation, when tumor volumes reach an approximate average of 200 mm³, mice are randomized into test groups according to tumor volume, and treated for 21 days with either control (no test compound) or test compound at one of three dosage levels: 10 mg/kg, 30 mg/kg or 100 mg/kg.

Data Analysis:

For each individual animal, body weight and tumor size [using the commonly accepted formula: Tumor Volume (mm³)=(a×b²/2); where ‘a’ represents the length, and ‘b’ the width of the tumor as determined by caliper measurements], are monitored twice weekly throughout the study. A sustained body weight loss greater than 15% of the initial body weight is considered as clinical toxicity, with the animal removed from the study and sacrificed. Clinical signs of toxicity include, but are not limited to, persistent anorexia or dehydration, posture, moribund, lethargy, hypothermia and/or laboured respiration (according to the UKCCCR guidelines for welfare of animals in experimental neoplasia

A time-course of tumor growth is expressed as median values, or normalized to initial tumor volume on the day treatment started and expressed as mean±SEM (8 to 10 animals per group). For pre-established tumors, relative tumor volumes is calculated for each mouse (treated tumor volume/tumor volume on day 0) and expressed as mean±SEM for each treatment group. Twenty-four hours after the last treatment, animals are sacrificed, tumors excised and weighed. The anti-tumor effect of test compound versus control is determined and represented by a bar chart of median values±25/75 and 10/90 percentiles. Statistical significance is indicated by one-sided p-values from Wilcoxon-Mann-Whitney analysis (Wilcoxon rank sum test), with p<0.05 considered statistically significant. Treatment/control (T/C) ratios are calculated based on final relative tumor volumes, using the NCI criteria—“The effective criteria for T/C ratios is 42%”.

Formulation Example 1 Solid, Oral Dosage Form

As a specific embodiment of an oral composition, 100 mg of the Compound #65, prepared as in Example 3, above is formulated with sufficient finely divided lactose to provide a total amount of 580 to 590 mg to fill a size 0 hard gel capsule.

While the foregoing specification teaches the principles of the present invention, with examples provided for the purpose of illustration, it will be understood that the practice of the invention encompasses all of the usual variations, adaptations and/or modifications as come within the scope of the following claims and their equivalents. 

1. A compound of formula (I)

wherein R¹ and R² are taken together with the carbon atom to which they are bound to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₈cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one to two R¹¹ groups; (b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one to two R¹¹ groups; and (c) 4 to 8-membered, saturated heterocyclyl; wherein the 4 to 8-membered, saturated heterocyclyl contains one heteroatom selected from the group consisting of O, S and N; wherein the S is optionally substituted with one to two oxo; wherein the N is substituted with R¹⁰; provided that the heteroatom is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 8-membered, saturated heterocyclyl is optionally substituted with one R¹¹ group, and further optionally substituted with one R¹² group; wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄ alkyl), —(C₂₋₄alkyl)-O-(C₁₋₄ alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —C(O)—NR^(A)R^(B), —C(O)—(C₁₋₃ alkyl)-NR^(A)R^(B), —C(O)—(C₁₋₄ alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)O—(C₁₋₄ alkyl), —SO₂—(C₁₋₄ alkyl), —SO₂—NR^(A)R^(B), phenyl, and 5 to 6-membered heteroaryl; wherein Z¹ is selected from the group consisting of —CH₂—, —O—, —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(A)R^(B), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, and fluorinated C₁₋₄alkoxy; wherein each R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄ alkyl, -(C₁₋₄ alkyl)-O-(C₁₋₄ alkyl), -(C₁₋₄ alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)-phenyl, —C(O)-(5 to 6-membered heteroaryl),

—C(O)OH, —C(O)O—(C₁₋₄alkyl), —SO₂—(C₁₋₄alkyl), —SO₂—NR^(D)R^(E), phenyl and, 5 to 6-membered heteroaryl; wherein Z² is selected from the group consisting of —CH₂—, —O—, —N(R^(C))—, —S—, —S(O)— and —SO₂—; wherein R^(D), R^(E) and R^(F) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; and wherein the phenyl or 5 to 6-membered heteroaryl whether alone or as part of a substituent group, is further optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, NR^(D)R^(E), C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, and fluorinated C₁₋₄alkoxy; and wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and hydroxy substituted C₁₋₄alkyl; m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-2S-yl, and piperidin-4-yl; a is an integer from 0 to 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR^(E)—, —C(S)—, —SO₂—, and —SO₂—NR^(L)—; wherein R^(E) is selected from the group consisting of hydrogen and C₁₋₄alkyl; R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), 4 to 6-membered, saturated heterocyclyl, —(C₁₋₄alkyl)-(4 to 6-membered, saturated heterocyclyl), —(C₂₋₄alkenyl)-(5 to 6-membered, saturated heterocyclyl), 5 to 6-membered heteroaryl, —(C₁₋₄alkyl)-(5 to 6-membered heteroaryl), —(C₂₋₄alkenyl)-(5 to 6-membered heteroaryl), and NR^(V)R^(W); wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein the C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, whether alone or as part of a substituent group, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₄alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 2; each R⁴ is independently selected from the group consisting of hydroxy, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, cyano, and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; provided that each R⁴ group is bound to a carbon atom; provided that when

is selected from the group consisting of

and substituted with —(R⁴)_(b), then b is an integer from 0 to 1; R⁵ is selected from the group consisting of

selected from the group consisting of aryl, heteroaryl, and partially unsaturated heterocyclyl; c is an integer from 0 to 2; each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄ alkyl, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-CN, —(C₁₋₄alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —NR^(M)R^(N), —(C₁₋₄alkyl)-NR^(P)R^(Q), —C(O)—(C₁₋₄ alkyl), —C(O)-(fluorinated C₁₋₂ alkyl), —C(O)—NR^(M)R^(N), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —NR^(M)—C(O)H, —NR^(M)—C(O)—(C₁₋₄alkyl), —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₆ cycloalkyl, -cyano-(C₃₋₆cycloalkyl), —(C₁₋₄alkyl)-(C₃₋₆cycloalkyl), —S—(C₃₋₆cycloalkyl), —SO—(C₃₋₆cycloalkyl), —SO₂—(C₃₋₆cycloalkyl), —NH—(C₃ ₋₆ cycloalkyl), —NH—SO₂—(C₃₋₆ cyclalkyl), oxetanyl, —(C₁₋₂ alkyl)-oxetanyl, tetrahydofuranyl, —(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl, and —(C₁₋₂alkyl)-tetrahydro-pyranyl; wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein R^(P) and R^(Q) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; alternatively R^(P) and R^(Q) are taken together with the nitrogen atom to which they are bound to form a 5 to 6-membered saturated heterocyclyl; such 5 to 6-membered saturated heterocyclyl is optionally substituted with a substituent selected from the group consisting of halogen, C₁₋₄alkyl, and fluorinated C₁₋₄alkyl;

wherein selected from the group consisting of phenyl and 5 to 6-membered heteroaryl; d is an integer from 0 to 1; R⁷ is selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(R)R^(S), —C(O)—NR^(R)R^(S), —C(O)OH and —C(O)O—(C₁₋₄alkyl); wherein R^(R) and R^(S) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein

is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl; e is an integer from 0 to 2; each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁ ₋₄alkyl), —(C₁ ₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, —(C₁₋₂alkyl)-oxetanyl, tetrahydofuranyl, —(C₁₋₂alkyl)-tetrahydro-furanyl, tetrahydro-pyranyl, and —(C₁₋₂alkyl)-tetrahydro-pyranyl; wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃ or —SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl) and 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl and 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than of indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 2. A compound as in claim 1, wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of (a) C₃₋₆cycloalkyl; wherein the C₃₋₈cycloalkyl is optionally substituted with one R¹¹ group; (b) benzo-fused C₅₋₆cycloalkyl; wherein the benzo-fused C₅₋₆cycloalkyl is bound through a carbon atom of the C₅₋₆cycloalkyl portion of the ring structure; and wherein the benzo-fused C₅₋₆cycloalkyl is optionally substituted with one R¹¹ group; and (c) 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered, saturated heterocyclyl contains O or NR¹⁰; provided that the O or NR¹⁰ is not present at the 2-position relative to the carbon atom of the imidazolin-5-one; and wherein the 4 to 6-membered, saturated heterocyclyl containing the O or NR¹⁰ is optionally substituted with one R¹¹ group and further optionally substituted with one R¹²; wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —CH₂-(hydroxy substituted C₁₋₄alkyl), —(C₂₋₄alkenyl), —(C₁₋₄alkyl)-phenyl, —(C₂alkyl)-O-(C₁₋₄alkyl), —C(O)O—(C₁₋₄alkyl), —C(O)—(C₁₋₄alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—(C₃₋₆cycloalkyl),

—C(O)—NR^(A)R^(B), and —SO₂—(C₁₋₂alkyl); wherein Z¹ is selected from the group consisting of —CH₂—, —O—, and —N(R^(C))—; and wherein R^(A), R^(B) and R^(C) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein R¹¹ is independently selected from the group consisting of hydroxy, oxo, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, hydroxy substituted C₁₋₄alkyl, —(C₁₋₄alkyl)-phenyl, -cyano, —NR^(D)R^(E), —C(O)—NR^(D)R^(E), —C(O)—(C₁₋₄alkyl), —C(O)OH, and —C(O)O—(C₁₋₄alkyl); wherein R¹² is selected from the group consisting of hydroxy, oxo, halogen, C₁₋₂alkyl, CF₃, C₁₋₂alkoxy, —OCF₃, and hydroxy substituted C₁₋₂alkyl; m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2, then m is 0;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3S-yl, piperidin-3R-yl, and and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)—NR^(L), and —SO₂—; wherein R^(L) is selected from the group consisting of hydrogen and methyl; R³ is selected from the group consisting of C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, C₂₋₄alkenyl, C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl and NR^(V)R^(W); wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; wherein the C₃₋₆cycloalkyl, 4 to 6-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl, is optionally substituted with one to two substituents independently selected from the group consisting of halogen, hydroxy, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, —(C₁₋₂alkyl)-OH, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(G)R^(H); wherein R^(G) and R^(H) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl;

is selected from the group consisting of

b is an integer from 0 to 1; R⁴ is selected from the group consisting of, halogen, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, and NR^(J)R^(K); wherein R^(J) and R^(K) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; provided that the R⁴ group is bound to a carbon atom; R⁵ is selected from the group consisting of

selected from the group consisting of aryl, heteroaryl and partially unsaturated heterocyclyl; c is an integer from 0 to 2; each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, nitro, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, cyano substituted (C₁₋₄alkyl), —(C₁₋₂ alkyl)-O—(C₁₋₄alkyl), C₁₋₄alkoxy, fluorinated C₁₋₄alkoxy, —SO₂—(C₁₋₄alkyl), —C(O)—(C₁₋₄ alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₄alkyl), C₃₋₅ cyclo alkyl, 1-cyano-(C₃₋₅ cyclo alkyl), -(C₁₋₂alkyl)-(C₃₋₅ cycloalkyl), —S—(C₃₋₅ cycloalkyl), —SO₂—(C₃₋₅ cycloalkyl), —NH—(C₃₋₅ cycloalkyl), —NH—SO₂—(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; wherein

is selected from the group consisting of phenyl and 5 to 6-membered heteroaryl; d is an integer from 0 to 1; R⁷ is selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄alkoxy, and fluorinated C₁₋₄alkoxy; wherein

is selected from the group consisting of phenyl, 5 to 6-membered saturated heterocyclyl and 5 to 6-membered heteroaryl; e is an integer from 0 to 2; each R⁸ is independently selected from the group consisting of hydroxy, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, C₁₋₄ alkoxy, fluorinated C₁₋₄alkoxy, —NR^(T)R^(U), —C(O)—NR^(T)R^(U), —C(O)OH, —C(O)O—(C₁₋₄alkyl), —(C₁₋₄alkyl)-NR^(T)R^(U), C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), oxetanyl, and tetrahydro-furanyl; wherein R^(T) and R^(U) are each independently selected from the group consisting of hydrogen and C₁₋₄alkyl; provided that when

is a 5-membered heteroaryl, then

is bound at the 3-position, relative to the point of attachment of the

to the

provided further than when

is phenyl or a 6-membered heteroaryl, then

is bound at the 3- or 4-position, relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃ and —SO₂—CH₃,

and b=0; then R⁵ is other quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, and 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 3. A compound as in claim 2, wherein R¹ and R² are taken together to form an optionally substituted ring structure selected from the group consisting of C₃₋₆cycloalkyl and 4 to 6-membered, saturated heterocyclyl; wherein the 4 to 6-membered saturated heterocyclyl contains Ne; provided that the NR¹° is not present at the 2-position relative to the carbon atom of the imidazolidin-5-one; wherein R¹⁰ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₂₋₄alkenyl, —CH₂-(hydroxy substituted C₁₋₂ alkyl), —CH₂-(phenyl), —(C₂ alkyl)-O—(C₁₋₂ alkyl), —C(O)—(C₁₋₄ alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)-(cyclopropyl), —C(O)O—(C₁₋₄alkyl), —C(O)—NR^(A)R^(B), and —SO₂—(C₁₋₂alkyl), wherein R^(A) and R^(B) are each independently selected from the group consisting of hydrogen and methyl; m is an integer from 0 to 1; and n is an integer from 0 to 2 provide that when n is 2, then m is 0

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3-yl, piperidin-3R-yl, piperidin-3S-yl, and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O—, and —SO₂—; R³ is selected from the group consisting of C₁₋₄alkyl, hydroxy substituted C₁₋₄alkyl, fluorinated C₁₋₂alkyl, C₂₋₄alkenyl, C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl, 5 to 6-membered heteroaryl, and NR^(V)R^(W); wherein the C₃₋₅cycloalkyl, 4 to 5-membered, saturated heterocyclyl or 5 to 6-membered heteroaryl are each optionally substituted with a substituent selected from the group consisting of halogen, hydroxy, C₁₋₂alkyl, (C₁₋₂alkyl)-OH, fluorinated C₁₋₂alkyl, cyano, and NH₂; and wherein R^(V) and R^(W) are each independently selected from the group consisting of hydrogen and methyl;

is selected from the group consisting of

b is an integer from 0 to 1; R⁴ is selected from the group consisting of halogen, C₁₋₂alkyl, and C₁₋₂alkoxy; R⁵ is selected from the group consisting of

selected from the group consisting of phenyl, naphthyl, 5 to 6-membered heteroaryl, 9 to 10-membered heteroaryl, and partially unsaturated 9 to 10-membered heterocyclyl; c is an integer from 0 to 2; each R⁶ is independently selected from the group consisting of hydroxy, oxo, halogen, cyano, C₁₋₄alkyl, fluorinated C₁₋₂alkyl, hydroxy substituted C₁₋₄alkyl, cyano-substituted C₁₋₂alkyl, —(C₁₋₂alkyl)-O—(C₁₋₂ alkyl), C₁₋₄ alkoxy, fluorinated C₁₋₂ alkoxy, —SO₂—(C₁₋₄alkyl), —CO²H, —C(O)O—(C₁₋₂alkyl), —C(O)—(C₁₋₂alkyl), —C(O)-(fluorinated C₁₋₂alkyl), —C(O)—NR^(M)R^(N), —NR^(M)R^(N), —NR^(M)—C(O)H, —NR^(M)—SO₂—(C₁₋₂ alkyl), C₃₋₅cycloalkyl, 1-cyano-cyclopropyl, —(C₁₋₂ alkyl)-(C₃₋₅cycloalkyl), —S—(C₃₋₅cycloalkyl), —SO₂—(C₃₋₅cycloalkyl), —NH—C(O)—(C₃₋₅cycloalkyl) —NH—SO₂—(C₃₋₅cycloalkyl), and oxetan-3-yl; and wherein R^(M) and R^(N) are each independently selected from the group consisting of hydrogen and C₁₋₂alkyl; wherein

is selected from the group consisting of phenyl and 6-membered, nitrogen containing heteroaryl; wherein

is selected from the group consisting of phenyl, 5 to 6-membered, saturated, nitrogen containing heterocylyl and 5 to 6-membered, nitrogen containing heteroaryl; e is an integer from 0 to 1; R⁸ is selected from the group consisting of halogen, C₁₋₄alkyl, C₃₋₅cycloalkyl, —(C₁₋₂alkyl)-(C₃₋₅cycloalkyl), and oxetanyl; provided that the

is bound at the 3- or 4-position of the

relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and —SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl), or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 4. A compound as in claim 3, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(ethenyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxy-ethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, tetrahydro-pyran-4,4-diyl, tetrahydro-furan-3,3-diyl, and 1-(methoxycarbonyl)-azetidin-3,3-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 2; provided that when n is 2 then m is 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, piperidin-3R-yl, piperidin-3S-yl, and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—; R³ is selected from the group consisting of methyl, ethyl, isopropyl, 1-hydroxyethyl, trifluoromethyl, 2,2,2-trifluoroethyl, 2-hydroxy-propan-2-yl. 3-hydroxy-2-methyl-propan-2-yl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, amino, dimethylamino, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, thiazol-2-yl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, oxetan-2-yl, oxetan-3-yl, 3-methyl-oxetan-3-yl, and pyridin-3-yl;

is selected from the group consisting of

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro, 3-fluoro, 2-chloro, 3-chloro, 2-methyl, 3-methyl, and 2-methoxy; R⁵ is selected from the group consisting of

is selected from the group consisting of 3-cyano-phenyl, 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2-fluoro-4-(1-cyano-cuclopropyl)-phenyl, 2-fluoro-5-trifluoromethyl-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-trifluoromethoxy-phenyl, 4-trifluoromethoxy-phenyl, 4-(methylcarbonyl)-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-amino-4-hydroxy-phenyl, 3-formamido-4-hydroxy-phenyl 3-(cyclopropylthio)-phenyl, 3-(cyclopropylsulfonyl)-phenyl, 3-(cyclopropylcarbonyl-amino)-phenyl, 3-(cyclopropylsulfonyl-amino)-phenyl, 3-(methylsulfonyl)-phenyl, 3-(isopropylsulfonyl)-phenyl, 3-(aminocarbonyl)-phenyl, 3-carboxy-phenyl, 3-(methoxycarbonyl)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropyloxy-naphth-2-yl, 2-cyano-naphth-7-yl, 6-cyano-naphth-2-yl, 7-cyano-naphth-2-yl, 5-methoxy-naphth-2-yl, 7-methoxy-naphth-2-yl, 1,5-naphthyridin-3-yl, 1,8-naphthyridin-2-yl, 1,8-naphthyridin-3-yl, chroman-6-yl, isochroman-6-yl, isochroman-7-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 6-isopropyl-pyridin-3-yl, 6-n-propyl-pyridin-3-yl, 5-bromo-pyridin-2-yl, 5-chloro-pyridin-3-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 6-cycloprpoyl-pyridin-3-yl, 6-(1-cyano-cyclopropyl)-pyridin-3-yl, 2-amino-pyrid-4-yl, 5-amino-pyridin-3-yl, 6-amino-pyridin-2-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, 1-(trifluoromethyl-carbonyl)-indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 3-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 7-bromo-quinolin-2-yl, 2-hydroxy-quinolin-3-yl, 2-cyano-quinolin-6-yl, 2-cyano-quinolin-7-yl, 6-cyano-quinolin-2-yl, 2-methyl-quinolin-5-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2,4-dimethyl-quinolin-7-yl, 2-chloro-3-methyl-quinolin-7-yl, 2-chloro-4-methyl-quinolin-7-yl, 2-methyl-8-fluoro-quinolin-2-yl, 2-methyl-quinolin-7-yl, 2-methyl-7-bromo-quinolin-7-yl, 3-methyl-7-bromo-quinolin-7-yl, 2-methyl-4-chloro-quinolin-7-yl, 4-methyl-7-bromo-quinolin-2-yl, 2-trifluoromethyl-quinolin-7-yl, 2-oxo-quinolin-7-yl, 2-carboxy-quinolin-7-yl, 2-aminocarbonyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 3-fluoro-isoquinolin-6-yl, 6-bromo-isoquinolin-3-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazlin-7-yl, quinoxalin-6-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 4-chloro-indazol-5-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,7-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 2-ethyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 2-isopropyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl, 1-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 2-(2-hydroxyethyl)-6-fluoro-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-5-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-7-methoxymethyl-indazol-4-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-7-hydroxymethyl-indazol-4-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 2-methyl-3-cyano-indazol-5-yl, 2-methyl-3-hydroxymethyl-indazol-5-yl, 2-methyl-3-methoxymethyl-indazol-5-yl, 1-(2-hydroxyethyl)-indazol-5-yl, 2-(2-hydroxyethyl)-indazol-5-yl), 1-(2-cyanoethyl)-indazol-5-yl, 2-(2-cyanoethyl)-indazol-5-yl, 1-oxetan-3-yl-indazol-5-yl, 1-cyclopropyl-indazol-5-yl, 1-cyclopropylmethyl-indazol-5-yl, 2-cyclopropylmethyl-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-2-yl, 1,2-dimethyl-benzimidazol-6-yl, 1-methyl-6-fluoro-benzimidazol-2-yl, 2-oxo-benzimidazol-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzisoxazol-5-yl, benzthiazol-2-yl, benzthiazol-5-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 5-chloro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 6-methyl-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydro-benzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, 1,2,3,4-tetrahydro-2-methylcarbonyl-isoquinolin-6-yl, 1,2,3,4,4a,8a-hexahydro-2-methyl-carbonyl-isoquinolin-6-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl, 1,2-dimethyl-1,2-dihydro-3-oxo-indazol-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, pyrrolo[2,3-b]pyridin-5-yl, 1-methyl-pyrazolo[4,3-b]pyridin-5-yl, [1,2,4]triazo[4,3-a]pyridin-6-yl, 3-methyl-[1,2,4]triazo[4,3-a]pyridin-6-yl, and 4-methyl-3,4-dihydro-pyrido[3,2-b][1,4]oxazin-7-yl;

is selected from the group consisting of phenyl, pyridin-3-yl, and pyridin-4-yl; and

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isopropyl-pyrazol-4-yl, 1-isobutyl-pyrazol-5-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-cyclopropylmethyl-pyrazol-3-yl, 1-cyclopropylmethyl-pyrazol-5-yl, 1,2,3,4-tetrazol-5-yl, pyrazol-3-yl, pyrrolidin-1-yl, morpholin-4-yl, 4-methyl-piperazin-1-yl, imidazol-1-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, and 1-(oxetan-3-yl)-pyrazol-4-yl; provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the point of attachment of the

to the

provided further that when

is pyridin-4-yl, then

is bound to

at the 3-position, relative to the point of attachment of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl, m is 1 and n is 0 or m is 0 and n is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and —SO₂—CH₃,

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl, 1-methyl-indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-(1-methyl-pyrazol-4-yl)-phenyl, 1,2, 3,4,4a, 8a-hexahydro -2-methyl-carbonyl-isoquinolin-6-yl, or 1,2,3,4-trihydro-2-methylcarbonyl-isoquinolin-2-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-pyrazol-4-yl, 4-methyl-3,4-dihydro-pyrido[2,3-b]oxazon-7-yl, 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —SO₂-pyrrolidin-1-yl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than benzofuran-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-isopropylsulfonyl-phenyl, 1-methyl-indazol-5-yl, 1-isopropyl-indazol-5-yl, 1-oxetan-3-yl, indazol-5-yl, 1-methyl-pyrazol-4-yl, 4-methyl-7-bromo-quinolin-2-yl, 5-(2-hydroxy-2-methyl-propyl)-pyridin-2-yl, 6-isopropyl-pyridin-3-yl, 6-(1-cyanomethyl)-pyridin-3-yl, 6-(2-hydroxy-2-methyl-propyl)-pyridin-3-yl, 1,5-naphthyridin-3-yl, 3-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl, 4-(1-isobutyl-pyrazol-5-yl)-phenyl, or 6-(morpholin-4-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl or piperidin-3S-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than indazol-5-yl, benzofuran-5-yl, benzothien-5-yl, 1-methyl-indazol-5-yl, 4-(4-methylphenyl)phenyl, or 4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-trifluoromethyl-phenyl, 1-methyl-pyrazol-4-yl, benzoxazol-5-yl, pyridin-4-yl or 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 5-chloro-pyridin-3-yl, 2-oxo-3,4-dihydro-quinolin-7-yl, or 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-thiazol-2-yl, —C(O)—CF₃, —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than quinolin-7-yl, 1-methyl-indazol-5-yl, benzofuran-5-yl, or 4-(1-methyl-pyrazol-4-yl)-phenyl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 5. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(ethenylcarbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, tetrahyrdofuran-3,3-diyl, and tetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3S-yl, and piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of ethyl, 1-hydroxy-ethyl, isopropyl, 2-hydroxy-propan-2-yl, 3-hydroxy-2-methyl-propan-2-yl, 2,2,2-trifluoroethyl, ethenyl, cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, 1-hydroxymethyl-cyclopropyl, 1-amino-cyclopropyl, cyclobutyl, 1-methyl-cyclobutyl, pyrrolidin-1-yl, 1-methyl-pyrazol-3-yl, oxetan-2-yl, oxetan-3yl, 3-methyl-oxetan-3-yl, tetrahydro-furan-2yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and dimethylamino;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl; R⁵ is

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-hydroxy-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2,4-dichloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-trifluoromethyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 3-aminocarbonyl-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 3-methylsulfonyl-amino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, 3-(cyclopropyl-sulfonyl)-phenyl, naphtha-2-yl, 6-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 5-methoxy-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-isopropoxy-naphth-2-yl, 6-cyano-naphth-2-yl, 7-methoxy-naphth-2-yl, 7-cyano-naphth-2-yl, 6-amino-pyridin-2-yl, isochroman-6-yl, isochroman-7-yl, 2-oxo-indolin-5-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 1,2-dimethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl-indol-5-yl), 3-cyanomethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 2-chloro-quinolin-7-yl, 4-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 3-chloro-quinolin-7-yl, 2-methyl-quinolin-6-yl, 2-methyl-quinolin-6-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, 2-chloro-3-methyl-quinolin-7-yl, isoquinolin-3-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 3-fluoro-isoquinolin-6-yl, 1-chloro-isoquinolin-6-yl, 3-chloro-isoquinolin-6-yl, 1-methoxy-isoquinolin-6-yl, 3-methoxy-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, 1-oxo-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 1-methyl-indazol-3-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-4-yl, 2-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indazol-5-yl, 1,4-dimethyl-indazol-5-yl, 1,8-dimethyl-indazol-5-yl, 1-ethyl-indazol-5-yl, 1-methyl-3-chloro-indazol-5-yl, 1-methyl-3-chloro-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-cyano-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-methoxy-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-hydroxymethyl-indazol-5-yl, 1-methyl-3-hydroxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, 1-(cyclopropylmethyl)-indazol-5-yl, benzofuran-5-yl, benzofuran-6-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzoxazol-2-yl, benzoxazol-5-yl, 6-chloro-benzoxazol-2-yl, benzimidazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, 2-oxo-benzimidazol-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 5-chloro-benzothiazol-2-yl, 5-fluoro-benzothiazol-2-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 5,6-difluoro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 2-methyl-benzothiazol-6-yl, 5-cyano-benzothiazol-2-yl, 6-cyano-benzthiazol-2-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothioen-5-yl, 2,3-dihydrobenzofuran-5-yl, 2-oxo-3,4-dihydro-quinolin-6-yl, benzo[1,3]dioxol-5-yl, 1,8-naphthyridin-2-yl, and pyrrolo[2,3-b]pyridin-5-yl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than quinolin-7-yl, benzofuran-5-yl or 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl, and indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-pyridin-3-yl;

(R⁴)_(b) is 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1,

is piperidin-4-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than benzoxazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 2-oxo-3,4-dihydro-quinolin-7-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 6. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, piperidin-4,4-diyl, 1-(methyl)-piperidin-4,4-diyl, 1-(isopropyl)-piperidin-4,4-diyl, 1-(2-hydroxy-ethyl)-piperidin-4,4-diyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(benzyl)-piperidin-4,4-diyl, 1-(methyl-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, 1-(cyclopropyl-carbonyl)-piperidin-4,4-diyl, 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl, 1-(trifluoromethyl-carbonyl)-piperidin-4,4-diyl, 1-(methyl-sulfonyl)-piperidin-4,4-diyl, 1-(2-methoxyethyl)-piperidin-4,4-diyl, 1-(methoxycarbonyl)azetidin-3,3-diyl, tetrahydro-furan-3,3-diyl, and tetrahydro-pyran-4,4-diyl; m is an integer from 0 to 1; and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl and piperidin-4-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of ethyl, cyclopropyl, 1-hydroxy-cyclopropyl, 1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxymethyl-cyclopropyl, cyclobutyl, tetrahydro-furan-2-yl, tetrahydro-furan-2R-yl, tetrahydro-furan-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, 2-methyl, 2-methoxy, 3-fluoro, and 3-methyl; R⁵ is

is selected from the group consisting of 4-cyano-phenyl, 3-hydroxy-phenyl, 4-fluoro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-fluoro-4-chloro-phenyl, 3-chloro-4-fluoro-phenyl, 2-fluoro-4-cyano-phenyl, 2,4-dichloro-phenyl, 3-methyl-phenyl, 4-methyl-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 4-dimethylamino-phenyl, 3-(cyclopropyl-sulfonylamino)-phenyl, 3-(cyclopropyl-carbonylamino)-phenyl, 3-(cyclopropyl-thio)-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-4-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 1-methyl-indol-6-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 2-(hydroxymethyl)-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-(cyanomethyl)-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, 2-oxo-indolin-5-yl, quinolin-2-yl, quinolin-3-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 8-fluoro-quinolin-7-yl, 4-methyl-quinolin-7-yl, 2-cyano-quinolin-6-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl, 6-fluoro-isoquinolin-6-yl, 1-amino-isoquinolin-6-yl, 3-amino-isoquinolin-6-yl, quinazolin-7-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-4-yl, 1-methyl-indazol-5-yl, 1-methyl-indazol-6-yl, 2-methyl-indazol-6-yl, 1,3-dimethyl-indaozl-5-yl, 1,4-dimethyl-indazol-5-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, 1-methyl-3-methoxymethyl-indazol-5-yl, 1-methyl-3-methoxymethyl-indazol-6-yl, 1-methyl-3-cyclopropyl-indazol-5-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, 2,3-dimethyl-benzofuran-5-yl, benzothiazol-2-yl, benzothiazol-5-yl, 6-fluoro-benzothiazol-2-yl, 6-chloro-benzothiazol-2-yl, 2-methyl-benzothiazol-5-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, and pyrrolo[2,3-b]pyridin-5-yl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than a compound selected from the group consisting of quinolin-7-yl, benzofuran-5-yl and 1-methyl-indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 7. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, 1-(methoxy-carbonyl)-piperidin-4,4-diyl, 1-(isopropyl-carbonyl)-piperidin-4,4-diyl, and 1-(dimethylamino-carbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrfuran-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro, 2-chloro, and 2-methyl; R⁵ is

is selected from the group consisting of 3-hydroxy-phenyl, naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-chloro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 8-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2,3-dimethyl-indol-5-yl, 3-cyanomethyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, quinolin-3-yl, quinolin-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, 2-cyano-quinolin-6-yl, isoquinolin-6-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothiazol-2-yl, benzthiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-5-yl, 1-methyl-benzimidazol-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, and 2,3-dimethyl-benzothien-5-yl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl or indazol-5-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 8. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro and 2-methyl; R⁵ is selected from the group consisting of

is selected from the group consisting of naphtha-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-5-yl, 2-hydroxymethyl-indol-5-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-2-yl, 8-fluoro-quinolin-2-yl, isoquinolin-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-cyano-benzofuran-5-yl, benzothien-5-yl, 2-methyl-benzothien-5-yl, 2,3-dimethyl-benzothien-5-yl, benzoxazol-2-yl, benzothiazol-2-yl, and 1-methyl-benzimidazol-5-yl; wherein

is selected from the group consisting of pyridin-4-yl and 1-methyl-pyrazol-4-yl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 9. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, and tetrahydropyran-4,4-diyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl, 1-fluoro-cyclopropyl, 1-hydroxy-cyclopropyl, 1-methyl-cyclopropyl, tetrahydrofuran-2-yl, tetrahydrofuran-2S-yl, and oxetan-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro and 2-methyl; R⁵ is selected from the group consisting of

is selected from the group consisting of naphth-2-yl, 6-chloro-naphth-2-yl, 6-fluoro-naphth-2-yl, 7-fluoro-naphth-2-yl, 8-fluoro-naphth-2-yl, 6-methyl-naphth-2-yl, 6-methoxy-naphth-2-yl, 6-cyano-naphth-2-yl, indol-3-yl, indol-5-yl, indol-6-yl, 1-methyl-indol-5-yl, 2-methyl-indol-6-yl, 3-(2-hydroxyethyl)-indol-5-yl, 3-cyanomethyl-indol-5-yl, 1,3-dimethyl-indol-5-yl, 1-methyl-3-(2-hydroxyethyl)-indol-5-yl, quinolin-7-yl, 3-chloro-quinolin-7-yl, 6-fluoro-quinolin-6-yl, isoquinolin-6-yl, quinazolin-7-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, 1-methyl-indazol-5-yl, 2-methyl-indazol-6-yl, 1-methyl-3-amino-indazol-6-yl, 1-methyl-3-aminocarbonyl-indazol-6-yl, benzofuran-5-yl, 2-methyl-benzofuran-5-yl, 2-methyl-benzothien-5-yl, benzothiazol-5-yl, 6-chloro-benzothiazol-2-yl, 6-methyl-benzothiazol-2-yl, 6-cyano-benzothiazol-2-yl, benzimidazol-5-yl, and 1-methyl-benzimidazol-5-yl; wherein

is selected from the group consisting of 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and pyridin-4-yl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl), and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 1-methyl-indazol-5-yl, indazol-5-yl, or 4-(1-isobutyl-pyrazol-5-yl)-phenyl; provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0,

is azetidin-3-yl; -(L¹)_(a)-R³ is —C(O)-(1-hydroxy-cyclopropyl);

and (R⁴)_(b) is 2-methyl; then R⁵ is other 1-methyl-indazol-5-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 10. A compound as in claim 4, wherein R¹ and R² are taken together to form cyclopropyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is cyclopropyl;

is selected from the group consisting of

b is 0; R⁵ is

is selected from the group consisting of indol-5-yl, indol-6-yl, indazol-4-yl, indazol-5-yl, 1-methyl-indazol-5-yl, benzthiazol-5-yl, benzofuran-5-yl, benzothien-5-yl, and 6-cyano-naphth-2-yl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 11. A compound as in claim 4, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl, cyclopentyl, tetrahydro-furan-3,3-diyl, tetrahydro-pyran-4,4-diyl, 1-(methoxycarbonyl)-azetidin-3,3-diyl, piperidin-4,4-diyl, 1-(isopropylcarbonyl)-piperidin-4,4-diyl, 1-(2-hydroxyethyl)-piperidin-4,4-diyl, 1-(dimethylamino-methylcarbonyl)-piperidin-4,4-diyl, 1-(methylsulfonyl)piperidin-4,4-diyl, and 1-(cyclopropylcarbonyl)-piperidin-4,4-diyl; m is an integer from 0 to 2; and n is an integer from 0 to 1; provided that when m is 2, then n is 0;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, pyrrolidin-3R-yl, piperidin-3R-yl, and piperidin-4-yl; a is 1; L¹ is selected from the group consisting of —C(O)—, —C(O)O— and —SO₂—; R³ is selected from the group consisting of methyl, 1-hydroxyethyl, trifluoromethyl, cyclopropyl, 1-methyl-cyclopropyl, 1-hydroxy-cyclopropyl, tetrahydro-furan-2R-yl, pyrrolidin-1-yl, and thiazol-2-yl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro and 2-methyl; R⁵ is

is selected from the group consisting of phenyl, pyridin-3-yl, pyridin-4-yl, and pyrazol-4-yl; and wherein

is selected from the group consisting of 4-bromo-phenyl, 3-chloro-phenyl, 4-methyl-phenyl, pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-3-yl, 1-(cyclopropylmethyl)-pyrazol-3-yl, 1-(2-methylpropyl)-pyrazol-3-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, 1-isobutyl-pyrazol-5-yl, 1-(cyclopropylmethyl)-pyrazol-5-yl, tetrazol-5-yl, 5-methyl-oxazdiazol-2-yl, piperazin-1-yl, 4-methyl-piperazin-1-yl, pyrrolidin-1-yl, morpholin-14-yl, imidazol-1-yl, and oxetan-3-yl; provided that when

is phenyl or pyridin-3-yl, then

is bound to

at the 4-position, relative to the binding position of the

to the

provided further that when

is pyridin-4-yl or pyrazol-4-yl, then

is bound to

at the 3-position, relative to the binding position of the

to the

provided that when R¹ and R² are taken together with the carbon atom to which they are bound to form 1-(methoxycarbonyl)-azetidin-3-yl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)-cyclopropyl, —C(O)-(thiazol-2-yl), —C(O)OCH₃, and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopentyl; m is 1 and n is 0 or m is 0 and m is 1;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

b=0 or (R⁴)_(b) is 2-methyl; then R⁵ is other than 2-(piperazin-1-yl)-pyridin-4-yl, or 2-(4-methyl-piperazin-1-yl)-pyridin-4-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 0, and

is azetidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)-cyclopropyl, —C(O)-(1-methyl-cyclopropyl) and —C(O)-(1-hydroxy-cyclopropyl);

b=0 or (R⁴)_(b) is selected from the group consisting of 2-fluoro and 2-methyl; then R⁵ is other than 4-(1-isobutyl-pyrazol-5-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0, n is 2,

is piperidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(4-methylphenyl)phenyl or 4-(3-chlorophenyl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 1, n is 1, and

is piperidin-4-yl; -(L¹)_(a)—R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form cyclopropyl; m is 0 and n is 1 or m is 1 and n is 0;

is pyrrolidin-3R-yl; -(L¹)_(a)-R³ is —C(O)-cyclopropyl;

and b=0; then R⁵ is other than 6-(4-methyl-piperazin-1-yl)-pyridin-3-yl; provided further that when R¹ and R² are taken together with the carbon atom to which they are bound to form tetrahydrofuran-3,3-diyl or tetrahydropyran-4,4-diyl; m is an integer from 0 to 1 and n is 0 or m is 0 and n is an integer from 0 to 1;

is selected from the group consisting of azetidin-3-yl, pyrrolidin-3R-yl, and pyrrolidin-3-yl; -(L¹)_(a)-R³ is selected from the group consisting of —C(O)—CF₃, —C(O)OCH₃ and —SO₂—CH₃;

and b=0; then R⁵ is other than 4-(1-methyl-pyrazol-4-yl)-phenyl; and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 12. A compound as in claim 10, wherein R¹ and R² are taken together to form a ring structure selected from the group consisting of cyclopropyl and cyclopentyl; m is an integer from 0 to 1; and n is 0;

is selected from the group consisting of azetidin-3-yl and pyrrolidin-3R-yl; a is 1; L¹ is —C(O)—; R³ is selected from the group consisting of cyclopropyl, 1-hydroxy-cyclopropyl, and 1-methyl-cyclopropyl;

b is an integer from 0 to 1; R⁴ is selected from the group consisting of 2-fluoro and 2-methyl; R⁵ is

and wherein

is selected from the group consisting of pyridin-3-yl, pyridin-4-yl, 1-methyl-pyrazol-4-yl, 1-isopropyl-pyrazol-4-yl, 1-cyclopropyl-pyrazol-4-yl, 1-cyclobutyl-pyrazol-4-yl, 1-methyl-pyrazol-5-yl, and 5-methyl-oxadiazol-2-yl; wherein

is bound to the

phenyl at the 4-position, relative to the point of attachment of the

phenyl to the

and a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof.
 13. A compound as in claim 1, selected from the group consisting of 5-[4-(1-Benzofuran-5-yl)phenyl]-6-{[1-(cyclopropylcarbonyl)azetidin-3-yl]methyl}-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-(4-(6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-7-oxo-4,6-diazaspiro[2.4]hept-4-en-5-yl)-3-fluorophenyl)-2-naphthonitrile; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-methyl-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 5-(4-(benzo[d]thiazol-2-yl)-2-fluorophenyl)-6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(2-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; 6-((1-(cyclopropanecarbonyl)azetidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; and stereoisomers, tautomers and pharmaceutically acceptable salts thereof.
 14. A compound as in claim 1, selected from the group consisting of 6-{[1-(Cyclopropylcarbonyl)azetidin-3-yl]methyl}-5-[4′-(1-methyl-1H-pyrazol-4-yl)biphenyl-4-yl]-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(Cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(4′-(1-methyl-1H-pyrazol-4-yl)-[1,1′-biphenyl]-4-yl)-4,6-diazaspiro[2.4]hept-4-en-7-one; (R)-6-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-5-(2-fluoro-4-(1-methyl-1H-indazol-5-yl)phenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one; and stereoisomers, tautomers and pharmaceutically acceptable salts thereof.
 15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim
 1. 16. A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier. 17.-25. (canceled)
 26. A compound as in claim 1 for use as a medicament.
 27. A compound as in claim 1 for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme.
 28. A compound as in claim 1, for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, the disorder selected from the group consisting of cancer of the breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood and bone.
 29. A compound as in claim 1, for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme, the disorder selected from the group consisting of (a) obesity and related disorders and (b) liver related disorders.
 30. A composition comprising a compound as in claim 1, for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme.
 31. A composition comprising a compound as in claim 1, for use in the treatment of a disorder mediated by inhibition of fatty acid synthase (FASN) enzyme the disorder selected from the group consisting of (a) cancer selected from the group consisting of breast, prostate, head, neck, skin, lung, ovary, endometrium, thyroid, colon, rectum, esophagus, stomach, kidney, liver, bladder, pancreas, brain, spinal cord, blood, and bone; (b) obesity or a related disorder selected from the group consisting of obesity, overweight, weight gain, Type II diabetes mellitus, Syndrome X, and appetite or satiety modulation; and (c) a liver related disorders selected from the group consisting of dyslipidemia, elevated cholesterol levels, elevated LDL, decreased HDL, elevated triglicerides, fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver and non-alcoholic fatty liver disease (NAFLD). 32.-35. (canceled) 